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Neurodegenerative diseases (NDs), characterized by progressive degeneration and death of neurons, are strongly related to aging, and the number of people with NDs will continue to rise. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common NDs, and the current treatments offer no cure. A growing body of research shows that AD and especially PD are intricately related to intestinal health and the gut microbiome and that both diseases can spread retrogradely from the gut to the brain. Zeolites are a large family of minerals built by [SiO4]4− and [AlO4]5− tetrahedrons joined by shared oxygen atoms and forming a three-dimensional microporous structure holding water molecules and ions. The most widespread and used zeolite is clinoptilolite, and additionally, mechanically activated clinoptilolites offer further improved beneficial effects. The current review describes and discusses the numerous positive effects of clinoptilolite and its forms on gut health and the gut microbiome, as well as their detoxifying, antioxidative, immunostimulatory, and anti-inflammatory effects, relevant to the treatment of NDs and especially AD and PD. The direct effects of clinoptilolite and its activated forms on AD pathology in vitro and in vivo are also reviewed, as well as the use of zeolites as biosensors and delivery systems related to PD. [ABSTRACT FROM AUTHOR]

LA or (±)-α-Lipoic acid (6,8-thioctic acid, 5-(1,2-dithiolan-3-yl)pentanoic acid) (LA) is a heterocyclic thia fatty acid consisting of pentanoic acid and a 1,2-dithiolan-3-yl group at the 5-position. LA is an amphiphilic pharmacophore with excellent antioxidant, anti-inflammatory and neuroprotective effects attested by numerous studies for its potential utility in both the treatment and diverse forms of prophylaxis of neurodegenerative disorders, especially Alzheimer's disease. This article aims to assess the differences in neuroprotective effect after short-term (11 days) and longterm (51 days) LA administration in an experimental rat model of scopolamine-induced dementia by correlating biochemical data on acetylcholinesterase activity with behavioural data. Behaviourally appraised changes in learning and memory appear to correlate with biochemical changes in AChE activity. The neuroprotective effect of LA, as ascertained by its beneficial effects on learning and memory in a scopolamine animal model, appears to be associated with cholinergic mechanisms (a decrease in AChE activity), and to be larger after short-term administration rather than long-term administration. These results further underscore the candidacy of LA as a viable drug candidate suitable for continued investigation and derivate synthesis endeavours. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder classically characterized by two neuropathological hallmarks: β-amyloid plaques and tau tangles in the brain. However, the cellular and molecular mechanisms involved in AD are still elusive, which dampens the possibility of finding new and more effective therapeutic interventions. Current in vitro models are limited in modelling the complexity of AD pathogenesis. In this study, we aimed to characterize the AD expression signature upon a meta-analysis of multiple human datasets, including different cell populations from various brain regions, and compare cell-specific alterations in AD patients and in vitro models to highlight the appropriateness and the limitations of the currently available models in recapitulating AD pathology. The meta-analysis showed consistent enrichment of the Rho GTPases signaling pathway among different cell populations and in the models. The accuracy of in vitro models was higher for neurons and lowest for astrocytes. Our study underscores the particularly low fidelity in modelling down-regulated genes across all cell populations. The top enriched pathways arising from meta-analysis of human data differ from the enriched pathways arising from the overlap. We hope that our data will prove useful in indicating a starting point in the development of future, more complex, 3D in vitro models. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a complex neurodegenerative disease with multifactorial etiology, unsatisfactory treatment, and a necessity for broad-spectrum active substances for cure. The mucus from Helix aspersa snail is a mixture of bioactive molecules with antimicrobial, anti-inflammatory, antioxidant, and anti-apoptotic effects. So far there are no data concerning the capacity of snail extract (SE) to affect neurodegenerative disorders.Objective: The effects of SE from Helix aspersa on learning and memory deficits in Alzheimer's type dementia (ATD) induced by scopolamine (Sco) in male Wistar rats were examined and some mechanisms of action underlying these effects were evaluated.Methods: SE (0.5 mL/100 g) was applied orally through a food tube for 16 consecutive days: 5 days before and 11 days simultaneously with Sco (2 mg/kg, intraperitoneally). At the end of Sco treatment, using behavioral methods, we evaluated memory performance. Additionally, in cortex and hippocampus the acetylcholinesterase (AChE) activity, acetylcholine and monoamines (dopamine, noradrenaline, and serotonin) content, levels of main oxidative stress markers, and expression of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) were determined.Results: We demonstrated that, according to all behavioral tests used, SE significantly improved the cognitive deficits induced by Sco. Furthermore, SE possessed AChE inhibitory activity, moderate antioxidant properties and the ability to modulate monoamines content in two brain structures. Moreover, multiple SE applications not only restored the depressed by Sco expression of CREB and BDNF, but significantly upregulated it.Conclusion: Summarizing results, we conclude that complex mechanisms underlie the beneficial effects of SE on impaired memory in Alzheimer's type dementia. [ABSTRACT FROM AUTHOR]

In this work, we develop a new approach based on differential scanning calorimetry (DSC) for diagnostics and characterization of the changes in the brain at molecular and supramolecular level associated with drug-induced neurodegenerative disorders. In order to test the DSC potential, we used an experimental animal model of scopolamine-induced dementia of Alzheimer's disease (AD) type. The DSC measurements taken on supernatants of brain tissue homogenates isolated from healthy animals and animals with scopolamine-induced dementia showed that heat capacity curves for animals with scopolamine-induced dementia strongly differ from the respective curves for healthy animals. The effects of preventive treatments with various substances and their combinations expected to have protective effect and hinder the development of AD (myrtenal, ellagic acid, lipoic acid, ascorbic acid) are also clearly displayed in the calorimetric scans. These measurements show that DSC is an appropriate method for detection and characterization of the compositional changes taking place in affected by dementia brain tissues. [ABSTRACT FROM AUTHOR]

Differential scanning calorimetry was applied to evaluate the efficacy of preventive treatments with biologically active compounds of plant origin against neurodegenerative disorder in mice. As we reported recently, large differences exist between the heat capacity profiles of water-soluble brain proteome fractions from healthy animals and from animals with scopolamine-induced dementia: the profiles for healthy animals displayed well expressed exothermic event peaking at 40–45 °C, by few degrees above body temperature, but still preceding in temperature the proteome endothermic denaturational transitions; the low-temperature exotherm was completely abolished by the scopolamine treatment. Here we explored this signature difference in the heat capacity profiles to assess the efficacy of preventive treatments with protectant drugs anticipated to slow down or block progression of dementia (myrtenal, ellagic acid, lipoic acid and their combinations, including also ascorbic acid). We found that these neuroprotectants counteract the scopolamine effect and partially or completely preserve the ‘healthy’ thermogram, and specifically the low-temperature exotherm. These results well correlate with the changes in the cognitive functions of the animals assessed using the Step Through Test for learning and memory. The exothermic event is deemed to be associated with a reversible process of fibrillization and/or aggregation of specific water-soluble brain protein fractions preceding their denaturation. Most importantly, the results demonstrate that the effect of scopolamine and its prevention by protectant substances are clearly displayed in the heat capacity profiles of the brain proteome, thus identifying DSC as a powerful method in drug testing and discovery. [ABSTRACT FROM AUTHOR]

Differential scanning calorimetry (DSC) has been employed to examine the thermal behavior of brain tissues affected by a drug-induced neurodegenerative disorder. An animal (mouse) model of scopolamine-induced dementia was used. The DSC measurements performed on supernatants of brain tissue homogenates revealed large differences between the heat capacity profiles for healthy animals and for animals with scopolamine-induced dementia. The heat capacity profiles of the supernatants from healthy animals displayed well expressed exothermic transitions peaking in the range 35–45 °C, thus preceding in temperature the endothermic denaturational transitions. No such exothermic transitions were found in other samples from the same animals, e.g., centrifugation sediments of brain homogenates, liver homogenates, blood plasma. Remarkably, the low-temperature exotherms were completely abolished by the scopolamine treatment. The exothermic events may possibly reflect a process of aggregation of specific protein fractions in the brain supernatants. The reported findings may be important for the elucidation of the molecular mechanisms of cognitive impairment. [ABSTRACT FROM AUTHOR]