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Previously we were able to isolate by simple and mild methods from an aqueous sheep pineal extract an inhibiting principle acting on the anterior hypophysis of male rats in vitro. This substance could be located by paper electrophoresis. In the present paper we describe the further purification of this active principle by paper chromatography in two different solvents. In two regions possessing a special fluorescence an inhibiting factor of the gonadotropic activity of the anterior pituitary was found in vitro. [ABSTRACT FROM AUTHOR]

The development of new molecular and neurobiological methods, computer-assisted quantification techniques and neurobiological investigation methods which can be applied to the human brain, all have evoked an increased demand for post-mortem tissue in research. Psychiatric disorders are considered to be of neurobiological origin. Thus far, however, the etiology and pathophysiology of schizophrenia, depression and dementias are not well understood at the cellular and molecular level. The following will outline the consensus of the working group for neuropsychiatric brain banking organized in the Brainnet Europe II, on ethical guidelines for brain banking, clinical diagnostic criteria, the minimal clinical data set of retrospectively analyzed cases as well as neuropathological standard investigations to perform stageing for neurodegenerative disorders in brain tissue. We will list regions of interest for assessments in psychiatric disorder, propose a dissection scheme and describe preservation and storage conditions of tissue. These guidelines may be of value for future implementations of additional neuropsychiatric brain banks world-wide. [ABSTRACT FROM AUTHOR]

Acetic acid extracts of bovine pineals and cerebral cortex were separated on Sephadex G-25 columns. Subsequently two low molecular weight fractions, F and F, were ultrafiltered through the membranes UM2 and UM05. The UM05 residues were gel filtered on Sephadex G-15 columns or chromatographed on Dowex W50-X4 columns. Fractions from these columns were tested and those which showed COH-inhibiting activity were separated by preparative paper chromatography in different solvents. The absorption spectra of those fractions were recorded and tested for COH-inhibition. By these methods, a COH-inhibitor was localized in three different solvents. Some active paper chromatography fractions were studied in high pressure, reverse phase, liquid chromatography. This latter method showed that the active fractions obtained by paper chromatography contain several orthophthalaldehyde (OPT) positive compounds. [ABSTRACT FROM AUTHOR]

The potential of using wearable technologies for the objective assessment of motor symptoms in Parkinson's disease (PD) has gained prominence recently. Nonetheless, compared to tremor and gait impairment, less emphasis has been placed on the quantification of bradykinesia and rigidity. This review aimed to consolidate the existing research on objective measurement of bradykinesia and rigidity in PD through the use of wearables, focusing on the continuous monitoring of these two symptoms in free-living environments. A search of PubMed was conducted through a combination of keyword and MeSH searches. We also searched the IEEE, Google Scholar, Embase, and Scopus databases to ensure thorough results and to minimize the chances of missing relevant studies. Papers published after the year 2000 with sample sizes greater than five were included. Studies were assessed for quality and information was extracted regarding the devices used and their location on the body, the setting and duration of the study, the "gold standard" used as a reference for validation, the metrics used, and the results of each paper. Thirty-one and eight studies met the search criteria and evaluated bradykinesia and rigidity, respectively. Several studies reported strong associations between wearable-based measures and the gold-standard references for bradykinesia, and, to a lesser extent, rigidity. Only a few, pilot studies investigated the measurement of bradykinesia and rigidity in the home and free-living settings. While the current results are promising for the future of wearables, additional work is needed on their validation and adaptation in ecological, free-living settings. Doing so has the potential to improve the assessment and treatment of motor fluctuations and symptoms of PD more generally through real-time objective monitoring of bradykinesia and rigidity. [ABSTRACT FROM AUTHOR]

Bovine pineal glands were extracted according to the methods reported by Bensinger et al. (1973) and Cheesman and Fariss (1970). Isobutanol soluble COH-inhibiting activity was further separated by chromatography on Sephadex G-15 and paper chromatography. With the Bensinger method, different active pineal fractions were obtained from Sephadex G-15 columns. Certain of those fractions were further separated by paper chromatography in butanol: acetic acid: water (4∶1∶1) and the COH-inhibitor was localized. The pineal COH-inhibitor could also be localized by high pressure, reverse phase liquid chromatography. More COH-inhibiting activity was extracted with the Bensinger method than with aqueous and acetic acid extraction methods used earlier by us. The Cheesman extraction method for arginine vasotocin gave less regular results in our hands than the Bensinger extraction method. [ABSTRACT FROM AUTHOR]

The classic monoamine oxidase inhibitors (MAOIs) tranylcypromine (TCP) and phenelzine (PLZ) are powerful antidepressants that come with an equally powerful stigma, and are thus rarely prescribed—despite their well-established effectiveness. Some of these preconceptions appear to stem from unclarity, as the etiology of a rare but important side effect, 'spontaneous hypertension' (SH)—a significant increase in blood pressure absent dietary tyramine ingestion—remains improperly elucidated. This paper aims at uprooting some of the stigma surrounding MAOIs by advancing the trace amine (TA) theory as the causative underpinning of SH. This theory posits that SH results from the considerable influx of TAs observed following TCP- or PLZ-administration. TAs are known, albeit at greatly supraphysiological levels, to raise blood pressure on account of their propensity to exert potent indirect sympathomimetic effects; additionally, some research posits that TAs may induce vasoconstrictive effects partly or wholly separate therefrom, which would then constitute a second hypertensive mechanism. TAs are endogenous to the human body in low quantities. Both TCP and PLZ cause marked elevations of 2-phenylethylamine (PEA), meta- and para-tyramine (m-/p-TYR), octopamine (OA), and tryptamine (TRYP), following both acute and (sub)chronic administration. This paper holds that TYR plays a pivotal role in causing SH, due to its strong pressor effect. Cautious treatment of SH is advised, given its typically self-limiting nature. The risk of hypotensive overshoots must be taken into account. For severe cases, this paper urges reconsideration, following suitable confirmation trials, of antipsychotics (notably risperidone) as these agents may reduce striatal p-TYR levels. [ABSTRACT FROM AUTHOR]

Aqueous extracts of sheep pineal bodies were separated on Sephadex G-25. Two low molecular weight Sephadex G-25 fractions, F 2 and F 3, were ultrafiltrated through the Amicon membrane UM-2. The UM-2 filtrate was subsequently filtrated through the ultramembrane UM-05 and the UM-05 filtrate was separated on Sephadex G-10 columns. After paper electrophoresis, preparative paper chromatography was carried out. The fluorescent band showing a Rf value identical with synthetic 6-biopterin was eluted; gas liquid chromatography and mass spectrometry of the isolated compound were carried out. The mass spectra of the isolated compound were shown to be identical with synthetic 6-biopterin. The results of the Crithidia fasciculata test and thinlayer chromatography study revealed that the isolated compound is identical with 6-L-erythro-biopterin. The activities of the isolated compound and of synthetic biopterin in in vitro and in vivo bioassays are demonstrated. [ABSTRACT FROM AUTHOR]

For a special issue, we review studies on the pathogenesis of nigral cell death and the treatment of sporadic Parkinson's disease (sPD) over the past few decades, with a focus on the studies performed by Prof. Mizuno and our group. Prof. Mizuno proposed the initial concept that mitochondrial function may be impaired in sPD. When working at Jichi Medical School, he found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with Parkinson's disease (PD) and MPTP models. After moving to Juntendo University as a professor and chairman, he continued to study the mechanisms of cell death in the substantia nigra of patients with sPD. Under his supervision, I studied the relationships between PD and apoptosis, PD and iron involvement, mitochondrial dysfunction and apoptosis, and PD and neuroinflammation. Moving to Kitasato University, we focused on PD and the cytotoxicity of alpha synuclein (αSyn) as well as brain neuropathology. Eventually, I moved to Osaka University, where I continued working on PD and αSyn projects to promote therapeutic research. In this paper, we present the details of these studies in the following order: past, present, and future. [ABSTRACT FROM AUTHOR]

Parkinson's disease is characterized by its distinct pathological features; loss of dopamine neurons in the substantia nigra pars compacta and accumulation of Lewy bodies and Lewy neurites containing modified α-synuclein. Beneficial effects of L-DOPA and dopamine replacement therapy indicate dopamine deficit as one of the main pathogenic factors. Dopamine and its oxidation products are proposed to induce selective vulnerability in dopamine neurons. However, Parkinson's disease is now considered as a generalized disease with dysfunction of several neurotransmitter systems caused by multiple genetic and environmental factors. The pathogenic factors include oxidative stress, mitochondrial dysfunction, α-synuclein accumulation, programmed cell death, impaired proteolytic systems, neuroinflammation, and decline of neurotrophic factors. This paper presents interactions among dopamine, α-synuclein, monoamine oxidase, its inhibitors, and related genes in mitochondria. α-Synuclein inhibits dopamine synthesis and function. Vice versa, dopamine oxidation by monoamine oxidase produces toxic aldehydes, reactive oxygen species, and quinones, which modify α-synuclein, and promote its fibril production and accumulation in mitochondria. Excessive dopamine in experimental models modifies proteins in the mitochondrial electron transport chain and inhibits the function. α-Synuclein and familiar Parkinson's disease-related gene products modify the expression and activity of monoamine oxidase. Type A monoamine oxidase is associated with neuroprotection by an unspecific dose of inhibitors of type B monoamine oxidase, rasagiline and selegiline. Rasagiline and selegiline prevent α-synuclein fibrillization, modulate this toxic collaboration, and exert neuroprotection in experimental studies. Complex interactions between these pathogenic factors play a decisive role in neurodegeneration in PD and should be further defined to develop new therapies for Parkinson's disease. [ABSTRACT FROM AUTHOR]

Genetic and environmental factors increase autism spectrum disorder (ASD) incidence, and this has led to the generation of corresponding animal models, with some showing strong construct and face validity. This short review focuses on results we have recently obtained with environmental and genetic mouse models of ASD and that are the valproic acid, the poly I:C and the Shank 3 models. This has allowed us to provide a comparative description of these widely used animal models providing an interesting perspective as to the pros and cons of each one of them, in our experimental settings. In these papers, we focused on motor and gait disorders which are currently not included in the diagnosis criteria, but which may provide new insights to ASD pathophysiology potentially leading to innovative therapies for a disease that currently has none. In all these models, we reported behavioral, cellular and molecular alterations related to the cerebellum. Motor and gait deficits were observed to various degrees in animal models and, when strongly present, they were correlated to the severity of social deficits as well as to the number of cerebellar Purkinje cells. Additionally, we also reported that, like in humans, males are more severely affected than females in these ASD models. These findings, along with an increasing body of literature, open new hopes in the ASD field pointing to brain regions, such the cerebellum, that are at the crossroads between cognitive, social and motor deficits. Targeting these brain regions and their underlying pathways and synaptic connections may prove of significant benefits. [ABSTRACT FROM AUTHOR]

Pineal glands from adult, male rats were incubated in oxygenated Krebs-Ringer buffer containingC-cystine. After three hours the incubation media and pineal gland extracts were placed separately on Dowex AG W50-X-4 columns. In the elution volume whereC-labeled taurine is found a labeled peak was recovered. However, when subjected to one or two dimensional paper chromatography especially the eluants from pineal gland extracts yielded twoC-labeled substances one located in the region where unlabeled taurine is detected by ortho-phthalaldehyde reagent. These results were confirmed utilizing a method developed in our laboratory based on high performance liquid chromatography (HPLC). The pineals, as well as their respective incubation medium, were shown to contain radioactive taurine. These results demonstrate that rat pineal glands are capable of taurine synthesis. Also a high degree of labeling was associated with an area on paper chromatograms, migrating more rapidly than the standards, using acidic solvent systems. If represented by a single pineal compound, the substance must be rapidly synthesized fromC-cystine to account for the radioactivity observed. Future studies of sulfur metabolism within the pineal gland could be of significant interest. [ABSTRACT FROM AUTHOR]

Aqueous extracts of sheep pineals are separated on Sephadex G-25. The low molecular weight Sephadex G-25 fractions with antigonadotropic activity are ultrafiltered through the membrane UM 2. The UM 2 filtrate is subsequently filtered through the membrane UM 05. The actions of the different fractions on the anterior hypophysis and hypothalamus are discussed. The fractions which show an activity are further separated on Sephadex G-10. The active Sephadex G-10 fractions of the UM 05 filtrate acting on the anterior hypophysis in vitro are purified by electrophoresis and paper chromatography. After elution of different fluorescence bands the main inhibitory activity is found in a region, with the same Rf value as synthetic 6-biopterin. Gas liquid chromatography and mass spectrometry studies of the isolated fractions are carried out. The mass spectrum of an isolated compound from that fraction is identical with that of synthetic 6-biopterin. Thinlayer chromatography and the results of the Crithidia fasciculata test reveal that the isolated compound is probably identical with 6-L-erythrobiopterin. The activity of the active paper chromatography fraction (C) is compared with the activity of three synthetic biopterin-preparations in vitro and in vivo. The metabolic activities of biopterin derivatives and other pteridines are discussed. [ABSTRACT FROM AUTHOR]

Sexual dysfunction (SD) is a common, yet under-reported non-motor symptom of PD. Common sexual symptoms among male PD patients include erectile dysfunction, premature ejaculation, and decreased sexual desire. Few research papers have examined sexual dysfunction in PD, especially in YOPD male patients, and there is no Indian research study on sexual dysfunction in YOPD. In this study, we determined the frequency of sexual dysfunction in men with YOPD, and its correlation with other motor and NMS. This prospective cross-sectional study was conducted on YOPD males who presented to the Department of Neurology, NIMHANS, Bangalore, India, from May 2021 to April 2023. The diagnosis of YOPD was made based on MDS criteria for IPD 2015. Sexual functions were evaluated by ASEX, PEDT, QUIP-RS, and sex hormone assay. The patients also underwent other motor and non-motor assessments. Statistical analysis was done using SPSS version 22.0. The study was funded by the PDMD fund. This study included 62 male YOPD patients. The mean age of cases was 44.74 ± 8.54 years. The mean duration of symptoms was 8.45 ± 6.23 years. 43.5% of the cases of PD were Akinetic rigid type. By ASEX Score grading, 46.8% of the cases had erectile dysfunction and 71% of the cases of YOPD had premature ejaculation by PEDT Score grading. 9.7% of the cases had hypersexuality by QUIP-RS. Duration of YOPD was a better predictor of Erectile Dysfunction and premature ejaculation when compared with other variables. SD was related to anxiety and depression and it had a negative impact on the patient's health-related quality of life (HR-QoL). SD should be investigated and treated as an integral part of the neurological assessment in YOPD. [ABSTRACT FROM AUTHOR]

The regulation of cerebral blood flow (CBF) is a complex and tightly controlled function ensuring delivery of oxygen and nutrients and removal of metabolic wastes from brain tissue. Cerebral vasoreactivity (CVR) refers to the ability of the nervous system to regulate CBF according to metabolic demands or changes in the microenvironment. This can be assessed through a variety of nuclear medicine and imaging techniques and protocols. Several studies have investigated the association of CVR with physiological and pathological conditions, with particular reference to the relationship with cognitive impairment and cerebrovascular disorders (CVD). A better understanding of the interaction between CVR and cognitive dysfunction in chronic and particularly acute CVD could help improving treatment and rehabilitation strategies in these patients. In this paper, we reviewed current knowledge on CVR alterations in the context of acute and chronic CVD and cognitive dysfunction. Alterations in CVR and hemodynamics have been described in patients with both neurodegenerative and vascular cognitive impairment, and the severity of these alterations seems to correlate with CVR derailment. Furthermore, an increased risk of cognitive impairment progression has been associated with alterations in CVR parameters and hemodynamics. Few studies have investigated these associations in acute cerebrovascular disorders and the results are inconsistent; thus, further research on this topic is encouraged. [ABSTRACT FROM AUTHOR]

This paper examines the development of and some logistical and methodological issues surrounding the use of animal models of chronic pain. The first section addresses the emergent move towards mechanism-based and disease-related animal models of chronic pain that has accelerated since the late 1980s following publication of Bennett and Xie's (Pain 33:87–107, 1998) paper on chronic constriction injury of the sciatic nerve and Stein et al.'s (Pharmacol Biochem Behav 31:445–451, 1988) paper on unilateral hind paw inflammation with complete Freund's adjuvant. The discussion covers vast areas of chronic pain models developed over the past 50 years, starting with the numerous neuropathic, inflammatory and central pain models, as well as the growing number of models developed to study various forms of chronic pain from chronic back pain to visceral pain. It also examines the advantages and disadvantages of tonic pain models, mechanism-based and disease-related models of chronic pain, including issues related to the novel discovery of injury- or disease-related pathophysiological processes, the expansion of testing repertoires, and the successes and failures in the translation of analgesic development from animal preclinical models to human chronic pain conditions. The second section addresses experimental design considerations in the implementation of one of the 3Rs for the use of animal models of chronic pain; that is methods employed to reduce the number of animals used. The discussion covers various issues including the advantages and disadvantages of repeated dose designs and within-group drug testing, including incremental dosing schedules, and crossover designs. It also examines concerns surrounding the stability of symptoms and measures, including varying durations of multiple symptoms and the potential development of nociceptive sensitization, as well as possible use-dependent alterations in drug sensitivity and time-dependent changes in pain processes in specific animal models. [ABSTRACT FROM AUTHOR]

Research in Peter Riederer's lab in Vienna in the late 1970's came from a strong tradition in post-mortem neurochemical studies, at that time a relatively niche approach in neuroscience research. He was also early to recognise the value of post-mortem brain tissue in elucidating pharmacological mechanisms of neuropsychiatric treatments. I was fortunate to have Peter Riederer as a mentor in my early post-doctoral career; his generous support and the opportunities to use post-mortem brain tissue provided an invaluable grounding on which much of my future research was based. In this paper, I shall provide a brief overview of one trajectory of my research into the neurobiology of schizophrenia that started in the Riederer lab in Vienna investigating dopamine and the D2 receptor. Subsequent research to understand findings of increased dopamine resulted in the identification of reduced GABAergic innervation, culminating in the finding of a deficit in the parvalbumin-containing subtype of GABAergic neurons. Most recent work has been studying how changes in DNA methylation of the parvalbumin gene may relate to these findings in psychotic illness and its animal models. [ABSTRACT FROM AUTHOR]

Lab-on-chip technology is attracting great interest due to its potential as miniaturized devices that can automate and integrate many sample-handling steps, minimize consumption of reagent and samples, have short processing time and enable multiplexed analysis. Microfluidic devices have demonstrated their potential for a broad range of applications in life sciences, including point-of-care diagnostics and personalized medicine, based on the routine diagnosis of levels of hormones, cancer markers, and various metabolic products in blood, serum, etc. Microfluidics offers an adaptable platform that can facilitate cell culture as well as monitor their activity and control the cellular environment. Signaling molecules released from cells such as neurotransmitters and hormones are important in assessing the health of cells and the effect of drugs on their functions. In this review, we provide an insight into the state-of-art applications of microfluidics for monitoring of hormones released by cells. In our works, we have demonstrated efficient detection methods for bovine growth hormones using nano and microphotonics integrated microfluidics devices. The bovine growth hormone can be used as a growth promoter in dairy farming to enhance the milk and meat production. In the recent years, a few attempts have been reported on developing very sensitive, fast and low-cost methods of detection of bovine growth hormone using micro devices. This paper reviews the current state-of-art of detection and analysis of hormone using integrated optical micro and nanofluidics systems. In addition, the paper also focuses on various lab-on-a-chip technologies reported recently, and their benefits for screening growth hormones in milk. [ABSTRACT FROM AUTHOR]

Several indoles with mass spectra identical to those of synthetic melatonin, 5-hydroxyindole-3-acetic acid (5-HIAA), 5-methoxyindole-3-acetic acid (5-MIAA), 5-hydroxytryptophol (5-HTL) and 5-methoxy-tryptophol (5-MTL) could be located, isolated and identified in sheep pineal extracts using rather simple and mild extraction and separation methods. An antigonadotropin, which differs from melatonin, was isolated and partially purified from sheep pineals, using compensatory ovarian hypertrophy after unilateral ovariectomy as a bioassay. Antigonadotropic and gonadotropic compounds which differ from the indoles above mentioned could be located with the same methods. In vitro, these fractions act either on the hypothalamus or on the anterior pituitary. From the paper chromatograhy fraction, acting on the anterior pituitary in vitro, a compound could be isolated which is most probably identical with biopterin. In our opinion, however, this compound is not responsible for the antigonadotropic activity of the fraction, observed in vitro. Some pineal fractions showing an effect on the activity of the hypothalmus or anterior pituitary of male rats and mice in vitro, be also active in some experimental tumour models. A possible relationship between disorders in pteridine metabolism and neoplastic growth is discussed. [ABSTRACT FROM AUTHOR]

Background: Based on recent evidence, more than 200 susceptibility genes have been identified to be associated with autism until now. Correspondingly, cytogenetic abnormalities have been reported for almost every chromosome. While the results of multiple genes associated with risk factors for autism are still incomplete, this paper systematically reviews published meta-analyses and systematic reviews of evidence related to autism occurrence. Method: Literature search was conducted in the PubMed system, and the publication dates were limited between January 2000 and July 2020. We included a meta-analysis and systematic review that assessed the impact of related gene variants on the development of autism. After screening, this comprehensive literature search identified 31 meta-analyses and ten systematic reviews. We arranged the genes related to autism in the published studies according to the order of the chromosomes, and based on the results of a meta-analysis and systematic review, we selected 6 candidate genes related to ASD, namely MTHFR C677T, SLC25A12, OXTR, RELN, 5-HTTLPR, SHANK, including basic features and functions. In addition to these typical genes, we have also listed candidate genes that may exist on almost every chromosome that are related to autism. Results: We found that the results of several literature reviews included in this study showed that the MTHFR C667T variant was a risk factor for the occurrence of ASD, and the results were consistent. The results of studies on SLC25A12 variation (rs2056202 and rs2292813) and ASD risk were inconsistent but statistically significant. No association of 5-HTTLPR was found with autism, but when subgroup analysis was performed according to ethnicity, the association was statistically significant. RELN variants (rs362691 and rs736707) were consistent with ASD risk studies, but some of the results were not statistically significant. Conclusion: This review summarized the well-known ASD candidate genes and listed some new genes that need further study in larger sample sets to improve our understanding of the genetic basis of ASD, but sample size and heterogeneity remain major limiting factors in some genome-wide association studies. We also found that common genetic variants in some genes may be co-risk factors for autism or other neuropsychiatric disorders when we collated these results. It is worth considering screening for these mutations in clinical applications. [ABSTRACT FROM AUTHOR]

The hypothalamus and Locus Coeruleus (LC) share a variety of functions, as both of them take part in the regulation of the sleep/wake cycle and in the modulation of autonomic and homeostatic activities. Such a functional interplay takes place due to the dense and complex anatomical connections linking the two brain structures. In Alzheimer's disease (AD), the occurrence of endocrine, autonomic and sleep disturbances have been associated with the disruption of the hypothalamic network; at the same time, in this disease, the occurrence of LC degeneration is receiving growing attention for the potential roles it may have both from a pathophysiological and pathogenetic point of view. In this review, we summarize the current knowledge on the anatomical and functional connections between the LC and hypothalamus, to better understand whether the impairment of the former may be responsible for the pathological involvement of the latter, and whether the disruption of their interplay may concur to the pathophysiology of AD. Although only a few papers specifically explored this topic, intriguingly, some pre-clinical and post-mortem human studies showed that aberrant protein spreading and neuroinflammation may cause hypothalamus degeneration and that these pathological features may be linked to LC impairment. Moreover, experimental studies in rodents showed that LC plays a relevant role in modulating the hypothalamic sleep/wake cycle regulation or neuroendocrine and systemic hormones; in line with this, the degeneration of LC itself may partly explain the occurrence of hypothalamic-related symptoms in AD. [ABSTRACT FROM AUTHOR]

An in vitro human melanoma cell assay was used to work up the partial purification of (a) low molecular weight (MW) substance(s) from aqueous extracts of ovine pineal tissue shown to contain a growth-inhibiting activity. A combination of paper chromatography, ion-exchange and reversephase high performance liquid chromatography with post-column antitumor assay has been developed. This allows a specific identification of an ovine pineal factor (MW<500) which inhibits the growth of human melanoma cells in vitro. The substance was partially purified to about 1,000 times as compared to the IC-value of the starting material (retentate 5). The growth inhibition of human melanoma cells in culture was complete at a dose of 0.1 μg/ml of purified pineal factor(s). It was demonstrated that the activity of this pineal compound differs from some substances known to be present in the pineal, such as melatonin, serotonin, peridines and β-carbolines. The activity was not destroyed by treatment with proteolytic enzymes. [ABSTRACT FROM AUTHOR]

An antigonadotropic substance was partially purified from aqueous extracts of bovine pineal glands by methods of gel filtration, ultrafiltration and ion exchange chromatography. Two biological tests, viz. inhibition of compensatory ovarian hypertrophy and reduction of ventral prostate weight, were used to guide the purification. The partially purified antigonadotropin was characterized chemically using techniques of UV and fluorescence spectrometry, thin layer and paper chromatography, paper electrophoresis and amino acid analysis. The results reveal a diversity of ninhydrin-positive components present in the preparations, including free and peptide-bound amino acids, as well as other unidentified components, but not including any of the commonly occurring indoles, indoleamines or catecholeamines. One peptide, oxidized glutathione, was identified in the most purified material containing the biologically active principle yet pure, synthetric glutathione has no antigonadotropic activity in the biological tests utilized. Although the chemical nature of the bovine pineal antigonadotropin remains in question it may be purified by the methods described. The activity is thought to reside in the extremely small, perhaps trace quantities of residues derived. It is believed that large scale, preparative studies will be required for structural determination. [ABSTRACT FROM AUTHOR]

Aqueous extracts of sheep pineal bodies and sheep cerebral cortex were separated on Sephadex G-25 and G-10. Several distinct peaks could be distinguished showing excitation and fluorescence maxima resembling those of indoles. However, in sheep pineal extract one peak was observed with different excitation and fluorescence maxima which could not be observed in sheep cerebral cortex. Using two-dimensional thinlayer chromatography a substance designated A was isolated and purified, showing excitation maxima at 298 nm and 358 nm, and a fluorescence maximum at 440 nm. Rf values of this substance A in 7 different solvent systems in thinlayer chromatography are presented. The results of paper electrophoresis experiments are also described. [ABSTRACT FROM AUTHOR]

Early-onset dementia (EOD) is characterized by functionally impairing deterioration in memory, language, personality or visuospatial skills emerging under the age of 65. Cerebral functioning can be assessed by visual electroencephalography (EEG) interpretation. The aim of this systematic review is to evaluate the diagnostic utility of visual EEG in EOD focusing on Alzheimer's disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Medline, Embase, Scopus, Web of Knowledge, and Google Scholar were systematically searched for studies where EEGs were included in the diagnostic evaluation of patients with dementia under the age of 65. Each paper was quality assessed and the results grouped according to dementia cause with a narrative summary. 4,157 papers were screened, 12 studies met the eligibility criteria with a total of 965 patients. An abnormal EEG was common to all causes of EOD. EEG abnormalities are more severe in early-onset AD patients. EEG severity grade is independent of disease duration. Slow wave activity is common to all dementias, but is most prominent in DLB. Frontal intermittent rhythmic delta activity could be considered as supportive for the diagnosis of DLB as can a Grand Total EEG score of over 9.5. EEG is usually normal in FTD. Focal changes can be seen in advanced VAD. Studies employed small patient groups, varying diagnostic criteria, and only a minority of patient diagnoses was pathologically confirmed. EEG may be useful as an adjunct in the diagnosis of DLB and AD. Further prospective well-powered studies are required to investigate diagnostic utility more robustly. [ABSTRACT FROM AUTHOR]

Numerous papers report on connections between creative work and dementing illness, particularly in frontotemporal dementia (FTD), which may combine with motor neuron disease (FTD-MND). However, the emergence of FTD(-MND) patients' de novo artistic activities is rarely reported and underappreciated. Therefore, the present review summarizes relevant case studies' outcomes, capturing creativity's multifaceted nature. Here, we systematically searched for case reports by paying particular attention to the chronological development of individual patients' clinical symptoms, signs, and life events. We synoptically compared the various art domains to the pattern of brain atrophy, the clinical and pathological FTD subtypes. 22 FTD(-MND) patients were identified with creativity occurring either at the same time (41%) or starting after the disease onset (59%); the median lag between the first manifestation of disease and the beginning of creativity was two years. In another five patients, novel artistic activity was developed by a median of 8 years before the start of dementia symptoms. Artistic activity usually evolved over time with a peak in performance, followed by a decline that was further hampered by physical impairment during disease progression. Early on, the themes and objects depicted were often concrete and realistic, but they could become more abstract or symbolic at later stages. Emergent artistic processes may occur early on in the disease process. They appear to be a communication of inner life and may also reflect an attempt of compensation or "self-healing". The relative preservation of primary neocortical areas such as the visual, auditory, or motor cortex may enable the development of artistic activity in the face of degeneration of association cortical areas and subcortical, deeper central nervous system structures. It is crucial to understand the differential loss of function and an individual's creative abilities to implement caregiver-guided, personalized therapeutic strategies such as art therapy. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue concerning the molecular mechanisms of central nervous system injury.

Many pain conditions in patients tend to co-occur, influencing the clinical expressions of each other in various ways. This paper summarizes the main concurrent pain conditions by analyzing the major interactions observed. In particular, co-occurrence will be examined in: visceral pain (especially ischemic heart disease, irritable bowel syndrome, dysmenorrhea/endometriosis and urinary pain), fibromyalgia, musculoskeletal pain and headache. Two concurrent visceral pains from internal organs sharing at least part of their central sensory projection can give rise to viscero-visceral hyperalgesia, i.e., enhancement of typical pain symptoms from both districts. Visceral pain, headache and musculoskeletal pains (myofascial pain from trigger points, joint pain) can enhance pain and hyperalgesia from fibromyalgia. Myofascial pain from trigger points can perpetuate pain symptoms from visceral pain conditions and trigger migraine attacks when located in the referred pain area from an internal organ or in cervico-facial areas, respectively. The pathophysiology of these pain associations is complex and probably multifactorial; among the possible processes underlying the mutual influence of symptoms recorded in the associations is modulation of central sensitization phenomena by nociceptive inputs from one or the other condition. A strong message in these pain syndrome co-occurrence is that effective treatment of one of the conditions can also improve symptoms from the other, thus suggesting a systematic and thorough evaluation of the pain patient for a global effective management of his/her suffering. [ABSTRACT FROM AUTHOR]

Sialorrhoea is a common symptom in many neurological disorders. Recently, botulinum toxin has been introduced as a treatment for sialorrhoea, and in this paper, we review the evidence for its effectiveness. The publications on the topic were searched and reviewed independently by two authors using the scale developed by the Therapeutics and Technology Assessment subcommittee for the American Academy of Neurology. All papers identified in our search fulfilled were evaluated, and classified into 1 of the 4 levels of evidence. According to this scheme, the effectiveness of botulinum toxin A in the treatment of sialorrhoea is considered established (level A). Botulinum toxin B is considered probably effective in the treatment of sialorrhoea (level B). [ABSTRACT FROM AUTHOR]

Prof. DDr. Gregor K. Wenning, a renowned scientist and expert in movement disorders, passed away in 2024. He dedicated his career to researching Multiple System Atrophy (MSA) and related neurodegenerative diseases. Gregor's work focused on understanding the pathogenesis and pathophysiology of MSA, as well as developing diagnostic criteria and therapeutic options for the disorder. He was highly respected in the scientific community and received numerous awards for his research. Gregor's contributions to the field of neuroscience will be remembered and his papers will continue to be influential in the study of the human brain. [Extracted from the article]

The region of the pedunculopontine tegmental nucleus (PPTg) has been proposed as a novel target for deep brain stimulation (DBS) to treat levodopa resistant symptoms in motor disorders. Recently, the anatomical organization of the brainstem has been revised and four new distinct structures have been represented in the ventrolateral pontine tegmentum area in which the PPTg was previously identified. Given this anatomical reassessment, and considering the increasing of our experience, in this paper we revisit the value of DBS applied to that area. The reappraisal of clinical outcomes in the light of this revisitation may also help to understand the consequences of DBS applied to structures located in the ventrolateral pontine tegmentum, apart from the PPTg. The implantation of 39 leads in 32 patients suffering from Parkinson's disease (PD, 27 patients) and progressive supranuclear palsy (PSP, four patients) allowed us to reach two major conclusions. The first is that the results of the advancement of our technique in brainstem DBS matches the revision of brainstem anatomy. The second is that anatomical and functional aspects of our findings may help to explain how DBS acts when applied in the brainstem and to identify the differences when it is applied either in the brainstem or in the subthalamic nucleus. Finally, in this paper we discuss how the loss of neurons in brainstem nuclei occurring in both PD and PSP, the results of intraoperative recording of somatosensory evoked potentials, and the improvement of postural control during DBS point toward the potential role of ascending sensory pathways and/or other structures in mediating the effects of DBS applied in the ventrolateral pontine tegmentum region. [ABSTRACT FROM AUTHOR]

Rasagiline, a neuroprotective inhibitor of type B monoamine oxidase, prevented PK111195-induced apoptosis in SH-SY5Y cells through inhibition of mitochondrial apoptosis signaling (J Neural Transm 120:1539-1551, , J Neural Transm 122:1399-1407, ). This paper presents that PK11195 induced superoxide flashes, the transit production burst, mediated by cyclosporine A-sensitive membrane permeability transition. Rasagiline prevented superoxide flashes, calcium efflux, and cell death by PK11195. Regulation of the initial pore formation at the inner mitochondrial membrane was confirmed as the decisive mechanism of neuroprotection by rasagiline. [ABSTRACT FROM AUTHOR]

Rasagiline and selegiline, inhibitors of type B monoamine oxidase (MAO-B), protect neurons from cell death in cellular and animal models. Suppression of mitochondrial membrane permeabilization and subsequent activation of apoptosis cascade, and induction of anti-apoptotic, pro-survival genes are proposed to contribute the anti-apoptotic function. Rasagiline suppresses neurotoxin- and oxidative stress-induced membrane permeabilization in isolated mitochondria, but the mechanism has been not fully clarified. In this paper, regulation of the mitochondrial permeability transition pore by rasagiline and selegiline was examined in apoptosis induced by PK11195, a ligand of the outer membrane translocator protein 18 kDa (TSPO) in SH-SY5Y cells. The pore opening was quantitatively measured using a simultaneous monitoring system for calcium (Ca) and superoxide (O) (Ishibashi et al. in Biochem Biophys Res Commun 344:571-580, ). The association of the pore opening with Ca efflux and ROS increase was proved by the inhibition of Bcl-2 overexpression and cyclosporine A treatment. Potency to release Ca was correlated with the cytotoxicity of TSPO antagonists, PK11195, FGIN-1-27 and protoporphyrin IX, whereas a TSPO agonist, 4-chloro-diazepamine, did not significantly increase Ca or cause cell death. Rasagiline and selegiline inhibited mitochondrial Ca efflux through the mitochondrial permeability transition pore dose dependently. Ca efflux was confirmed as the initial signal in mitochondrial apoptotic cascade, and the suppression of Ca efflux may account for the neuroprotective function of rasagiline and selegiline. The quantitative measurement of Ca efflux can be applied to determine anti-apoptotic activity of neuroprotective compounds. The role of mitochondrial Ca release in neuronal death and also in neuroprotection by MAO-B inhibitors is discussed. [ABSTRACT FROM AUTHOR]

Millions of individuals around the world are afflicted with Parkinson’s disease (PD), a prevalent and incapacitating neurodegenerative disorder. Dr. Reichmann, a distinguished professor and neurologist, has made substantial advancements in the domain of PD research, encompassing both fundamental scientific investigations and practical applications. His research has illuminated the etiology and treatment of PD, as well as the function of energy metabolism and premotor symptoms. As a precursor to a number of neurotransmitters and neuromodulators that are implicated in the pathophysiology of PD, he has also investigated the application of tryptophan (Trp) derivatives in the disease. His principal findings and insights are summarized and synthesized in this narrative review article, which also emphasizes the challenges and implications for future PD research. This narrative review aims to identify and analyze the key contributions of Reichmann to the field of PD research, with the ultimate goal of informing future research directions in the domain. By examining Reichmann’s work, the study seeks to provide a comprehensive understanding of his major contributions and how they can be applied to advance the diagnosis and treatment of PD. This paper also explores the potential intersection of Reichmann’s findings with emerging avenues, such as the investigation of Trp and its metabolites, particularly kynurenines, which could lead to new insights and potential therapeutic strategies for managing neurodegenerative disorders like PD. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder, affecting millions of people and rapidly increasing over the last decades. Even though there is no intervention yet to stop the neurodegenerative pathology, many efficient treatment methods are available, including for patients with advanced PD. Neuroplasticity is a fundamental property of the human brain to adapt both to external changes and internal insults and pathological processes. In this paper we examine the current knowledge and concepts concerning changes at network level, cellular level and molecular level as parts of the neuroplastic response to protein aggregation pathology, synapse loss and neuronal loss in PD. We analyse the beneficial, compensatory effects, such as augmentation of nigral neurons efficacy, as well as negative, maladaptive effects, such as levodopa-induced dyskinesia. Effects of physical activity and different treatments on neuroplasticity are considered and the opportunity of biomarkers identification and use is discussed. [ABSTRACT FROM AUTHOR]

A survey of papers read during a workshop held in Vienna, 1977, is given showing that the pineal gland can be considered a model for research on neuroendocrine control mechanisms in neoplastic growth. From data obtained by different authors it can be concluded that the role of the pineal indole melatonin is very important in regard of the incidence and the development of tumours. On the basis of all the facts mentioned in this paper it is obvious that pineal gland activity should be included into the neuroendocrine factors studied in relation with oncogenic processes. For future research a number of experimental approaches, which need special emphasis, are recommended. [ABSTRACT FROM AUTHOR]

Generalized anxiety disorder (GAD) is a prevalent anxiety disorder, but is still poorly recognized in clinical practice. The aim of this review is to provide a coherent understanding of the functional neuroanatomy of GAD; second, to discuss the current theoretical cognitive models surrounding GAD; and finally to discuss the discrepancy between fundamental research and clinical practice and highlight several potential directions for future research in this domain. A systematic review of original papers investigating the neural correlates of DSM-IV and DSM-5 defined GAD samples was undertaken in Ovid literature search, PubMed, Medline, EMbase, PsycINFO, Google Scholar, and TRIP databases. Articles published between 2007 and 2018 were included. First, GAD seems to be characterized by limbic and (pre)frontal abnormalities. More specifically, GAD patients show difficulties in engaging the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) during emotional regulation tasks. Second, the involved brain areas appear to be characterized by heterogeneity possibly due to a variety of experimental designs and test subjects. Third, regarding the discrimination between GAD and other anxiety disorders via fMRI, results appear to be mixed. Studies report both GAD-specific activity and an inability to differentiate between GAD and other anxiety or mood disorders. The usage of different experimental tasks, test subjects, outcome measures and experimental designs limits the possibilities of generalizing results as well as conducting meta-analytical research. Certain theoretical models of GAD describe our understanding of this disorder and form the basis for treatment interventions. However, fMRI research thus far has failed to validate these models. To bridge the gap between fundamental research and clinical practice in GAD, we propose that fMRI researchers make an effort to validate the existing cognitive model of GAD. An alternative approach could be that new models would be based on current neuroimaging research as well as convergent research methods such as Heart Rate Variability (a bottom up approach). [ABSTRACT FROM AUTHOR]

Extrapyramidal movement disorders comprise hypokinetic-rigid and hyperkinetic or mixed forms, most of them originating from dysfunction of the basal ganglia (BG) and their information circuits that have been briefly reviewed in part 1 of the papers on neuropathology and pathogenesis of extrapyramidal movement disorders. The classification of hyperkinetic forms distinguishes the following: (1) chorea and related syndromes; (2) dystonias (dyskinesias); (3) tics and tourette disorders; (4) ballism; (5) myoclonic and startle disorders; and (6) tremor syndromes. Recent genetic and molecular classification distinguishes the following: (1) polyglutamine disorders (Huntington's disease and related disorders); (2) pantothenate kinase associated neurodegeneration; (3) Wilson's disease and related disorders; and (4) other hereditary neurodegenerations without hitherto detected genetic or specific markers. The diversity of phenotypes is related to the deposition of pathologic proteins in distinct cell populations, causing neurodegeneration due to genetic and environmental factors, but there is frequent overlap between various disorders. Their etiopathogenesis is still poorly understood but is suggested to result from an interaction between genetic and environmental factors, multiple etiologies, and noxious factors (protein mishandling, mitochondrial dysfunction, oxidative stress, excitotoxicity, energy failure, chronic neuroinflammation), being more likely than one single factor. Current clinical consensus criteria have increased the diagnostic accuracy of most neurodegenerative movement disorders, but for their definite diagnosis, histopathological confirmation is required. A timely overview of the neuropathology and pathogenesis of the major hyperkinetic movement disorders is presented. [ABSTRACT FROM AUTHOR]

This paper discusses difficulties of pharmacogenomic data integration into clinical practice. It emphasizes the need for developing simple and easy to use bioinformatics tools to help prescribers to rapidly access and use genetic data in clinical decision-making at the point of encounter. [ABSTRACT FROM AUTHOR]

Two separate lines of inquiry indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity, and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences and environmental exposures. This research considered together raises the intriguing hypothesis first advanced by Pluess and Belsky (Dev Psychopathol 23:29-38, 2011) that prenatal-stress fosters, promotes or “programs” postnatal developmental plasticity. In this paper, we review further evidence consistent with this proposition, including a novel animal study which experimentally manipulated both prenatal stress and postnatal rearing. Directions for future work focused on mechanisms mediating the plasticity-inducing effects of prenatal stress and the moderators of such effects are outlined. [ABSTRACT FROM AUTHOR]

This review appraises over 150 recent original papers reporting data that demonstrate the greatly reduced tyramine content of modern-day ‘foods’, about which the medical literature has a paucity of information. It discusses the cardiovascular pharmacology of tyramine and the characteristics, extent, risks, and treatment of the blood pressure increases that sometimes result from tyramine ingestion (the pressor response). In past decades, cheese was the only food associated with documented fatalities resulting from hypertension. Today, few foods contain problematically high tyramine levels, which is a result of changes in international food production techniques (especially the use of starter cultures), and hygiene regulations. Nowadays, even ‘matured’ cheeses are usually safe in healthy-sized portions. The mechanism by which tyramine may be produced in foods (by certain micro-organisms) is explained and hundreds of recent estimations of cheeses are reviewed. Numerous other previously inadequately documented foods are reviewed, including fish and soy sauces, salami-type sausages, dried meats, beers, wines, and various condiments. Evidence that the risk of harm from the pressor response has previously been overstated is reviewed, and the iatrogenic harms from hasty and aggressive treatment of hypertensive urgency are re-evaluated. Evidence now suggests that MAOIs are of comparable safety to many newer drugs and are straightforward to use. Previously held concerns about MAOIs are misplaced and some are of over-estimated consequence. The variability of pressor sensitivity to tyramine between individuals means that the knowledge and judgement of doctors, and some care, are still required. [ABSTRACT FROM AUTHOR]

Since the pioneering finding of Caspi and co-workers in 2002 that exposure to childhood maltreatment predicted later antisocial behaviour (ASB) in male carriers of the low-activity MAOA-uVNTR allele, frequent replication studies have been published. Two meta-analyses, one in 2006 and the other in 2014, confirmed the original findings by Caspi and co-workers. In the present paper, we review the literature, note some methodological aspects of candidate gene-environment interaction (cG×E) studies and suggest some future directions. Our conclusions are as follows. (1) The direction of the effect in a cG×E model may differ according to the positive and negative environmental background of the population. (2) There is a predictor-intersection problem such that when measuring one type of maltreatment in a person, other kinds of maltreatment often co-occur. Other forms of abuse are implicitly considered in statistical models; therefore, it is difficult to draw conclusions about the effects of timing and the severity of different forms of stressful life events in relation to ASB. (3) There is also an outcome-intersection problem because of the major intersection of ASB and other forms of mental health problems. It is likely that the G×E with MAOA is related to a common unmeasured factor. (4) For the G×E model, in which the effect of the gene on the outcome variable is dependent on other predictor variables, theoretically, hypothesis-driven statistical modelling is needed. [ABSTRACT FROM AUTHOR]

The respective first and last authors of this article, Mirko Bibl and Jens Wiltfang, would like to clarify the issue of the seeming duplicate publication of a figure in two articles. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s00702-021-02361-9 [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s00702-021-02356-6 [ABSTRACT FROM AUTHOR]

Investigations of brain complex integrative actions should consider beside neural networks, glial, extracellular molecular, and fluid channels networks. The present paper proposes that all these networks are assembled into the brain hyper-network that has as fundamental components, the tetra-partite synapses, formed by neural, glial, and extracellular molecular networks. Furthermore, peri-synaptic astrocytic processes by modulating the perviousness of extracellular fluid channels control the signals impinging on the tetra-partite synapses. It has also been surmised that global signalling via astrocytes networks and highly pervasive signals, such as electromagnetic fields (EMFs), allow the appropriate integration of the various networks especially at crucial nodes level, the tetra-partite synapses. As a matter of fact, it has been shown that astrocytes can form gap-junction-coupled syncytia allowing intercellular communication characterised by a rapid and possibly long-distance transfer of signals. As far as the EMFs are concerned, the concept of broadcasted neuroconnectomics (BNC) has been introduced to describe highly pervasive signals involved in resetting the information handling of brain networks at various miniaturisation levels. In other words, BNC creates, thanks to the EMFs, generated especially by neurons, different assemblages among the various networks forming the brain hyper-network. Thus, it is surmised that neuronal networks are the “core components” of the brain hyper-network that has as special “nodes” the multi-facet tetra-partite synapses. Furthermore, it is suggested that investigations on the functional plasticity of multi-partite synapses in response to BNC can be the background for a new understanding and perhaps a new modelling of brain morpho-functional organisation and integrative actions. [ABSTRACT FROM AUTHOR]

This paper reviews the major organizational features of calretinin interneurons in the dorsal striatum of rodents and primates, with some insights on the state of these neurons in Parkinson’s disease and Huntington’s chorea. The rat striatum harbors medium-sized calretinin-immunoreactive (CR+) interneurons, whereas the mouse striatum is pervaded by medium-sized CR+ interneurons together with numerous small and highly immunoreactive CR+ cells. The CR interneuronal network is even more elaborated in monkey and human striatum where, in addition to the small- and medium-sized CR+ interneurons, a set of large CR+ interneurons occurs. The majority of these giant CR+ interneurons, which are unique to the primate striatum, also display immunoreactivity for choline acetyltransferase (ChAT), a faithful marker of cholinergic neurons. The expression of CR and/or ChAT by the large striatal interneurons appears to be seriously compromised in Parkinson’s disease and Huntington’s chorea. The species differences noted above have to be considered to better understand the role of CR interneurons in striatal organization in both normal and pathological conditions. [ABSTRACT FROM AUTHOR]

Behavioural inflexibility and associated atypical learning behaviours are common clinical manifestations of the autism spectrum disorder (ASD) phenotype. Despite advances in our understanding of ASD, little research has been devoted to experimental interventions that might help to circumvent behavioural inflexibility in ASD. The current paper suggests that motivational locomotion in the form of wheel running can reduce behavioural inflexibility and learning impairments in an ASD rat model, and discusses how the strategy of reward-coupled locomotor activity may lead to clinical interventions for children with ASD. [ABSTRACT FROM AUTHOR]

Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The 'advanced' stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of 'advanced Parkinson's disease' (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of 'advanced' PD and also propose the term 'complex phase' Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference. [ABSTRACT FROM AUTHOR]

Multiple System Atrophy (MSA) and Parkinson's diseases (PD) are elite members of the α-synucleinopathy organization. Aberrant accumulations of the protein α-synuclein characterize them. A plethora of evidence indicates the involvement of these rogue inclusions in a cascade of events that disturb cellular homeostasis resulting in neuronal dysfunction. These two neurodegenerative diseases share many features both clinically and pathologically. Cytotoxic processes commonly induced by reactive free radical species have been associated with oxidative stress and neuroinflammation, frequently reported in both diseases. However, it appears they have characteristic and distinct α-synuclein inclusions. It is glial cytoplasmic inclusions in the case of MSA while Lewy bodies manifest in PD. This is probably related to the etiology of the illness. At present, precise mechanism(s) underlying the characteristic configuration of neurodegeneration are unclear. Furthermore, the "prion-like" transmission from cell to cell prompts the suggestion that perhaps these α-synucleinopathies are prion-like diseases. The possibility of some underlying genetic foul play remains controversial. But as major culprits of pathological processes or even single triggers of PD and MSA are the same—like oxidative stress, iron-induced pathology, mitochondriopathy, loss of respiratory activity, loss of proteasomal function, microglial activation, neuroinflammation—it is not farfetched to assume that in sporadic PD and also in MSA a variety of combinations of susceptibility genes contribute to the regional specificity of pathological onset. These players of pathology, as mentioned above, in a synergistic combination, are responsible for driving the progression of PD, MSA and other neurodegenerative disorders. Elucidating the triggers and progression factors is vital for advocating disease modification or halting its progression in both, MSA and PD. [ABSTRACT FROM AUTHOR]