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The pathogenesis of multiple sclerosis (MS) is not completely understood, but genetic factors, autoimmunity, inflammation, demyelination, and neurodegeneration seem to play a significant role. Data from analyses of central nervous system autopsy material from patients diagnosed with multiple sclerosis, as well as from studies in the main experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), suggest the possibility of a role of oxidative stress as well. In this narrative review, we summarize the main data from studies reported on oxidative stress markers in patients diagnosed with MS and in experimental models of MS (mainly EAE), and case–control association studies on the possible association of candidate genes related to oxidative stress with risk for MS. Most studies have shown an increase in markers of oxidative stress, a decrease in antioxidant substances, or both, with cerebrospinal fluid and serum/plasma malonyl-dialdehyde being the most reliable markers. This topic requires further prospective, multicenter studies with a long-term follow-up period involving a large number of patients with MS and controls. [ABSTRACT FROM AUTHOR]

Background/Objectives: Several studies have shown a relationship between vitamin D and migraine, including the association between decreased serum 25‐hydroxyvitamin D in patients with migraine and the positive effects of vitamin D supplementations in the therapy of this disease. Two single‐nucleotide variants (SNVs) vitamin D receptor (VDR) gene, VDR rs2228570, and VDR rs731236 have shown an association with migraine risk in a previous case–control association study, while an exome sequencing study identified a rare variant in GC vitamin D binding protein gene. This study aims to look for the association between several common variants in these two genes and the risk for migraine. Methods: We genotyped 290 patients diagnosed with migraine and 300 age‐matched controls using specific TaqMan assays for VDR rs2228570, VDR rs731236, VDR rs7975232, VDR rs739837, VDR rs78783628, GC rs7041, and GC rs4588 SNVs. Results: We did not find an association between these SNVs and the risk for migraine. None of these SNVs were related to the positivity of a family history of migraine or with the presence of aura. The VDR rs731236A allele showed a significant association with the triggering of migraine attacks by ethanol (Pc = 0.007). Conclusions: In summary, the results of the current study suggest a lack of association between common SNVs in the VDR and GC gene and the risk of developing migraine. The possible relationship between VDR rs731236 and the triggering of migraine episodes with ethanol deserves future studies. [ABSTRACT FROM AUTHOR]

The possible usefulness of alpha-synuclein (aSyn) determinations in peripheral tissues (blood cells, salivary gland biopsies, olfactory mucosa, digestive tract, skin) and in biological fluids, except for cerebrospinal fluid (serum, plasma, saliva, feces, urine), as a marker of several diseases, has been the subject of numerous publications. This narrative review summarizes data from studies trying to determine the role of total, oligomeric, and phosphorylated aSyn determinations as a marker of various diseases, especially PD and other alpha-synucleinopathies. In summary, the results of studies addressing the determinations of aSyn in its different forms in peripheral tissues (especially in platelets, skin, and digestive tract, but also salivary glands and olfactory mucosa), in combination with other potential biomarkers, could be a useful tool to discriminate PD from controls and from other causes of parkinsonisms, including synucleinopathies. [ABSTRACT FROM AUTHOR]

It is well known that coenzyme Q10 (CoQ10) has important antioxidant properties. Because one of the main mechanisms involved in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative diseases is oxidative stress, analysis of the concentrations of CoQ10 in different tissues of AD patients and with other dementia syndromes and the possible therapeutic role of CoQ10 in AD have been addressed in several studies. We performed a systematic review and a meta-analysis of these studies measuring tissue CoQ10 levels in patients with dementia and controls which showed that, compared with controls, AD patients had similar serum/plasma CoQ10 levels. We also revised the possible therapeutic effects of CoQ10 in experimental models of AD and other dementias (which showed important neuroprotective effects of coenzyme Q10) and in humans with AD, other dementias, and mild cognitive impairment (with inconclusive results). The potential role of CoQ10 treatment in AD and in improving memory in aged rodents shown in experimental models deserves future studies in patients with AD, other causes of dementia, and mild cognitive impairment. [ABSTRACT FROM AUTHOR]

Several papers have been published suggesting a probable role of inflammatory factors in the etiopathogenesis of migraine. In this study, we investigated the possible association between common variants in the LAG3/CD4 genes (both genes, which are closely related, encode proteins involved in inflammatory and autoimmune responses) in the risk of migraine in a cohort of Caucasian Spanish participants. For this purpose, the frequencies of CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants, using a specific TaqMan-based qPCR assay, were assessed in 290 patients diagnosed with migraine and in 300 healthy controls. The relationship of these variables with several clinical features of migraine was also analyzed. The frequencies of the analyzed LAG3/CD4 genotypes did not differ significantly between the two study groups and were not related to the sex, age at onset of migraine, family history of migraine, presence or absence of aura, or the triggering effect of ethanol on migraine episodes. These results suggest a lack of association between common variants in the LAG3/CD4 genes and the risk of developing migraine in the Caucasian Spanish population. [ABSTRACT FROM AUTHOR]

Several recent works have raised the possibility of the contribution of the lymphocyte activation gene 3 (LAG3) protein in the inflammatory processes of multiple sclerosis (MS). Results of studies on the possible association between LAG3 gene variants and the risk of MS have been inconclusive. In this study, we tried to show the possible association between the most common single nucleotide variants (SNVs) in the CD4 and LAG3 genes (these two genes are closely related) and the risk of MS in the Caucasian Spanish population. We studied the genotypes and allelic variants CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 in 300 patients diagnosed with MS and 400 healthy patients using specific TaqMan-based qPCR assays. We analyzed the possible influence of the genotype frequency on age at the onset of MS, the severity of MS, clinical evolutive subtypes of MS, and the HLADRB1*1501 genotype. The frequencies of the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants were not associated with the risk of MS and were unrelated to gender, age at onset and severity of MS, the clinical subtype of MS, and HLADRB1*1501 genotype. The results of the current study showed a lack of association between the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 SNVs and the risk of developing MS in the Caucasian Spanish population. [ABSTRACT FROM AUTHOR]

According to several studies, inflammatory factors could be related to the pathogenesis of idiopathic restless legs syndrome (RLS). In addition, RLS and Parkinson's disease (PD) have shown a possible relationship, and recent studies have shown an association between CD4 rs1922452 and CD4 rs951818 single nucleotide variants (SNVs) and the risk for PD. For these reasons, we investigated the possible association between common variants in the LAG3/CD4 genes (which encoded proteins involved in inflammatory and autoimmune responses) and the risk for RLS in a Caucasian Spanish population. We assessed the frequencies of CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants in 285 patients with idiopathic RLS and 350 healthy controls using a specific TaqMan-based qPCR assay. We also analyzed the possible influence of the genotypes' frequencies on several variables, including age at onset of RLS, gender, family history of RLS, and response to drugs commonly used in the treatment of RLS. We found a lack of association between the frequencies of genotypes and allelic variants of the 3 SNVs studied and the risk of RLS, and a weak though significant association between the CD4 rs1922452 GG genotype and an older age at onset of RLS. With the exception of this association, our findings suggest that common SNVs in the CD4/LAG3 genes are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people. [ABSTRACT FROM AUTHOR]

Background/Objectives: Several recent studies suggest a possible role of lymphocyte activation 3 (LAG3) protein. LAG3 can behave as an α‐synuclein ligand, and serum and cerebrospinal fluid‐soluble LAG3 levels have been proposed as a marker of Parkinson's disease (PD). In this study, we aimed to investigate whether there is an association between 3 common single‐nucleotide variations (SNVs) in the LAG3 gene and its closely related CD4 molecule gene and the risk of PD in a Caucasian Spanish population. Two of them have been previously associated with the risk of PD in Chinese females. Methods: We analysed genotypes and allele frequencies for CD4 rs1922452, CD4 951818 and LAG3 rs870849 SNVs, by using specifically designed TaqMan assays, in a cohort composed of 629 PD patients and 865 age‐ and gender‐matched healthy controls. Results: The frequencies of the CD4 rs1922452 A/A genotype, according to the dominant and recessive genetic models, and of the CD4 rs1922452/A allelic variant were significantly lower, and the frequencies of the CD4 rs951818 A/A genotype, according to the dominant genetic model, and of the CD4 rs951818/A allele, were significantly higher in PD patients than in controls. The differences were not significant after stratifying by sex. These two SNVs showed strong linkage. Regression models showed a lack of relation between the 3 SNVs studied and the age at onset of PD. Conclusions: These data suggest a possible role of CD4 rs1922452 and CD4 rs951818 polymorphisms in the risk of PD. [ABSTRACT FROM AUTHOR]

Coenzyme Q10 (CoQ10) has an important role as an antioxidant. Being that oxidative stress is one of the mechanisms involved in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative diseases, several studies addressed the concentrations of CoQ10 in the different tissues of patients with PD and other parkinsonian syndromes (PS), trying to elucidate their value as a marker of these diseases. Other studies addressed the potential therapeutic role of CoQ10 in PD and PS. We underwent a systematic review and a meta-analysis of studies measuring tissue CoQ10 concentrations which shows that, compared with controls, PD patients have decreased CoQ10 levels in the cerebellar cortex, platelets, and lymphocytes, increased total and oxidized CoQ10 levels in the cerebrospinal fluid and a non-significant trend toward decreased serum/plasma CoQ10 levels. Patients with multiple system atrophy (MSA) showed decreased CoQ10 levels in the cerebellar cortex, serum/plasma, cerebrospinal fluid, and skin fibroblasts. Patients with Lewy body dementia (LBD) showed decreased cerebellar cortex CoQ10, and those with progressive supranuclear palsy (PSP) had decreased CoQ10 levels in the cerebrospinal fluid. A previous meta-analysis of studies addressing the therapeutic effects of CoQ10 in PD showed a lack of improvement in patients with early PD. Results of the treatment with CoQ10 in PSP should be considered preliminary. The potential role of CoQ10 therapy in the MSA and selected groups of PD patients deserves future studies. [ABSTRACT FROM AUTHOR]

Background/objectives: Histamine has shown a possible role in the etiopathogenesis of migraine. It has been reported an association between some polymorphisms in the diamine oxidase (DAO) gene and migraine, especially in women. Two studies addressing DAO activity in migraine patients showed conflicting results. We investigated the possible relationship of serum DAO activity and histamine levels and 3 polymorphisms in the DAO gene with the risk for migraine. Methods: We studied the frequencies of DAO rs10156191, rs1049742 and rs1049793 genotypes and allelic variants in 298 migraine patients and 360 healthy controls (using a TaqMan‐based qPCR assay), and serum DAO activity and histamine levels in a subset of 99 migraine patients and 115 controls with strict exclusion criteria, and analysed the relationship of these variables with several clinical features of migraine. Results: The frequencies of the DAO genotypes and allelic variants analysed were similar in migraine patients and controls. Serum DAO activity was significantly higher in migraine patients (Vmax/Km 4.24 ± 2.93 vs. 3.60 ± 7.64, p < 0.001), especially in females (Vmax/Km 4.63 ± 2.96 vs. 3.18 ± 2.32, p < 0.0001), while serum histamine was similar in both study groups. Conclusion: Serum DAO activity was increased in patients with migraine, especially in females, while serum histamine levels were normal. None of the studied polymorphisms was associated with the risk for migraine. [ABSTRACT FROM AUTHOR]