Variants in the 3' End of SLC6A3 in Northwest Han Population with Parkinson's.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders in neurology. It is possible that multifactorial and genetic factors are related to its pathogenesis. Recently, there have been reports of SLC6A3 genetic variants leading to PD. However, the role of 3' end of SLC6A3 in PD is less studied in different ethnic groups. To explore the roles of 3' end of SLC6A3 in PD development, 17 SNP sites in 3' end of SLC6A3 were analyzed in 360 PD patients and 392 normal controls of Han population residing in northwest of China. The significant difference of gene type and allele frequencies between the PD and control groups was detected only in rs40184 (P = 0.013 and 0.004, respectively; odds ratio 2.529, 95% confidence interval 1.325-4.827). The genotype and allele frequencies of the other 16 SNP sites were not found to be different between the PD group and the control group. rs2550936, rs3776510, and rs429699 were selected to construct the haplotypes; no significant difference was found in a frequency of 5 haplotypes between the PD group and the control group. These results suggest that the SLC6A3 variant in rs40184 A allele may increase the risk of PD in northwest Han population and may be a biomarker of PD.

Synergetic Neuroprotective Effect of Docosahexaenoic Acid and Aspirin in SH-Y5Y by Inhibiting miR-21 and Activating RXRα and PPARα.

Parkinson's disease (PD) is a serious neurodegenerative disorder that lacks effective therapeutic methods. In this research, expressions of PPARα, RXRα, and miR-21 were evaluated in PD patients and normal controls. To investigate the effects of miR-21, docosahexaenoic acid (DHA) and aspirin (ASA) on PD, as well as the relationships between them, SH-Y5Y cells were treated with DHA, ASA, or both for 24 h. The assay showed that levels of miR-21 were increased and levels of PPARα were decreased in PD patients compared with normal controls. miR-21 was negatively correlated with PPARα in PD patients. DHA and ASA could activate RXRα and PPARα, respectively. Additionally, DHA upregulated PPARα expression by inhibiting miR-21 in SH-Y5Y cells. A combination of DHA and ASA efficiently enhanced heterodimer formations of PPARα and RXRα and increased the expression of neurotrophic factors PSD-95, brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), while inhibiting NFκB and COX2. These findings suggest that a combination of DHA and ASA could significantly improve the expression of PSD-95, BDNF, and GDNF by promoting heterodimerization of PPARα and RXRα, thus supplying a new therapeutic method for PD.

IL-22 promotes Fas expression in oligodendrocytes and inhibits FOXP3 expression in T cells by activating the NF-κB pathway in multiple sclerosis.

Multiple sclerosis (MS) is characterized by an increase in interleukin-22 and Fas, and a decrease in FOXP3, among other factors. In this study, we examined patients with MS and healthy control subjects and used the experimental autoimmune encephalomyelitis (EAE) animal model to identify the effects of IL-22 on oligodendrocytes and T cells in MS development. In MS, the expression of Fas in oligodendrocytes and IL-22 in CD4+CCR4+CCR6+CCR10+ T cells was enhanced. Ikaros and FOXP3 were both decreased in T cells. Depending on exogenous IL-22, Fas increased the phosphorylation of mitogen- and stress-activated protein kinase 1 and activated the nuclear factor-κB pathway in oligodendrocytes, leading to an increase in Fas and oligodendrocyte apoptosis. IL-22 decreased FOXP3 expression by activating NF-κB, and it further inhibited PTEN and Ikaros expression. Tregs reversed the functions of IL-22. Taken together, these findings help to elucidate the mechanisms of IL-22 in MS development.