GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE: ACTIVITY INHIBITION AND PROTEIN OVEREXPRESSION IN ROTENONE MODELS FOR PARKINSON'S DISEASE
GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE: ACTIVITY INHIBITION AND PROTEIN OVEREXPRESSION IN ROTENONE MODELS FOR PARKINSON'S DISEASE
复制标题
3-磷酸甘油醛脱氢酶：帕金森病鱼藤酮模型中的活性抑制和蛋白质过度表达
DOI：
10.1016/j.neuroscience.2011.06.050
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发表时间：
2011-09-29
期刊：
影响因子：
3.3
通讯作者：
Wang，T.
中科院分区：
文献类型：
--
作者：
Huang，J.;Xiong，N.;Wang，T.
鱼藤酮是一种广泛使用的杀虫剂，是帕金森病(PD)的环境危险因素，可导致帕金森病大鼠模型黑质纹状体损伤、路易体样包涵体和帕金森症状。我们以前的研究表明，在鱼藤酮诱导的PC12(大鼠肾上腺嗜铬细胞瘤细胞)细胞死亡中，3-磷酸甘油醛脱氢酶(GAPDH)的过度表达和糖酵解的抑制是并存的。然而，目前还不清楚GAPDH过表达是否在体内的多巴胺能神经退行性变中起作用。在本研究中，我们发现在以鱼藤酮为基础的帕金森病动物模型中，黑质多巴胺能神经元中GAPDH的过度表达和阳性的路易体聚集，而黑质的GAPDH糖酵解活性降低。此外，GAPDH基因敲除显著降低了PC12中鱼藤酮的毒性。这些体外和体内数据表明，GAPDH在帕金森病的发病机制中起到了作用，可能为帕金森病的神经保护策略和替代治疗提供了一个新的分子靶点。
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.