Vinpocetine regulates levels of circulating TLRs in Parkinson's disease patients.

BACKGROUND: The pathogenesis of Parkinson's disease (PD) is complex; it includes mitochondrial dysfunction, oxidative stress, and neuroinflammation. Notably, Toll-like receptors (TLRs) may activate inflammatory or anti-inflammatory responses in Parkinson's disease. Vinpocetine has been tested as an anti-inflammatory in both animal and in vitro research. Thus, it is important to test whether the anti-inflammatory properties of vinpocetine may have a protective effect in PD patients. METHODS: Eighty-nine Parkinson's disease patients and 42 healthy controls were recruited for this study. All patients were randomly assigned to either the traditional therapy group (T PD group, n = 46) or the vinpocetine group (V PD group, n = 43), in a blinded manner. Both treatments were administered for 14 days. RESULTS: Administration of vinpocetine reduced mRNA levels of TLR2/4, as well as protein levels of the downstream signalling molecules, MyD88 and NF-κB; moreover, it lowered the expression levels of serum inflammatory cytokines, TNF-α and MCP-1. Notably, vinpocetine increased TLR3 mRNA levels, as well as protein levels of the downstream signalling molecules TRIF-ß and IRF-3, and serum levels of the anti-inflammatory cytokines IL-10 and IL-8. Furthermore, vinpocetine produced a robust increase in the Mini Mental State Examination score, compared to that achieved by using levodopa therapy. CONCLUSION: Vinpocetine treatment may exhibit anti-inflammatory activity and alleviate cognitive impairment.

GAPDH rs1136666 SNP indicates a high risk of Parkinson's disease.

BACKGROUND: Development of Parkinson's disease (PD) is attributed to both genetic and environmental factors. Furthermore,GAPDH may play a key role in the development of neurodegenerative disease. Examination of genetic polymorphism in patients with sporadic PD will help uncover the mechanisms of PD pathogenesis and provide new insights into the treatment of PD. METHODS AND RESULTS: The SNaPshot method was applied to determine the gene sequences in 265 patients with idiopathic PD and 269 control cases (sex- and age-matched). The rs1136666 polymorphism of GAPDH was determined to be closely associated with PD. Subsequently, the CC genotype of the rs1136666 fragment was transfected into SH-SY5Y cells via a plasmid. The genetic expression of rs1136666 CC could induce SH-SY5Y cell injury and apoptosis via regulation of the oxidant-antioxidant and apoptosis-antiapoptosis balance. rs1136666 CC of the GAPDH had a pro-apoptotic effect similar to that of rotenone, and combination of the rs1136666 CC genetic variation and the rotenone neurotoxic effect could aggravate oxidative stress, cell injury, and apoptosis better than either single treatment alone. CONCLUSION: This study confirmed that the rs1136666 CC allele of theGAPDH increased the risk of PD, particularly in older male patients.