title: Glyceraldehyde-3-phosphate dehydrogenase: activity inhibition and protein overexpression in rotenone models for Parkinson's disease.
abstract: 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.
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors: J
authors: J
authors: Huang
authors: N
authors: N
authors: Xiong
authors: C
authors: C
authors: Chen
authors: J
authors: J
authors: Xiong
authors: M
authors: M
authors: Jia
authors: Z
authors: Z
authors: Zhang
authors: X
authors: X
authors: Cao
authors: Z
authors: Z
authors: Liang
authors: S
authors: S
authors: Sun
authors: Z
authors: Z
authors: Lin
authors: T
authors: T
authors: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055785:Gene Knockdown Techniques; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D007150:Immunohistochemistry; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000201:enzymology* / Q000503:physiopathology; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity*; D014475:Uncoupling Agents / Q000633:toxicity*
chemical_list: D034741:RNA, Small Interfering; D014475:Uncoupling Agents; D012402:Rotenone; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases