miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP-Intoxicated SH-SY5Y Cells.

miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson's disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3 (GSK3) was upregulated at mRNA and protein levels in MPP-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF- and IL-1 in SH-SY5Y cells in the presence of MPP. Luciferase reporter assay demonstrated that GSK3 was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3 activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3 in MPP-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.