Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperGlyceraldehyde-3-phosphate dehydrogenase: activity inhibition and protein overexpression in rotenone models for Parkinson's disease

Rotenone, a widely used pesticide and an environmental risk factor for Parkinson's disease (PD), induces nigrostriatal injury, Lewy body-like inclusions, and Parkinsonian symptoms in rat models for PD. Our previous data indicated that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) overexpression and glycolytic inhibition were co-current in rotenone-induced PC12 (rat adrenal pheochromocytoma cells) cell death. However, whether GAPDH overexpression plays any role in dopaminergic neurodegeneration in vivo remains unknown. In this study, we have found that GAPDH overexpression and GAPDH-positive Lewy body-like aggregates in nigral dopaminergic neurons while nigral GAPDH glycolytic activity decreases in rotenone-based PD animal models. Furthermore, GAPDH knockdown reduces rotenone toxicity significantly in PC12. These in vitro and in vivo data suggest that GAPDH contributes to the pathogenesis of Parkinson's disease, possibly representing a new molecular target for neuroprotective strategies and alternative therapies for PD.

▶GAPDH expression was up-regulated in rotenone-induced PD models. ▶GAPDH glycolytic activity was decreased in rotenone-induced PD models. ▶GAPDH overexpression was associated with dopaminergic neuron degeneration. ▶GAPDH knockdown reduced rotenone toxicity significantly in the PC12 model.