Activation of the ATF2/CREB-PGC-1α pathway by metformin leads to dopaminergic neuroprotection.

ABSTRACT: Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN). Consistent with this data, metformin increased mitochondrial marker proteins in SH-SY5Y neuroblastoma cells. Mitochondrial protein expression by metformin was found to be brain region specific, with metformin

SUBMITTER: Kang H 

PROVIDER: S-EPMC5564711 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature