Abstract:
Parkinsons disease (PD) is a chronic fast growing neurodegenerative disorder of Central Nervous System (CNS) characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and formation of Lewy bodies (LBs) which causes dopamine deficiency within basal ganglia leading to motor and non-motor manifestation. According to reports, many factors are responsible for pathogenesis of PD which includes environmental factors, genetic factors, and aging factors. Whereas death of dopaminergic neurons is also caused by oxidative stress, neuroinflammation, and autophagy disorder. Molecular chaperones/co-chaperones are proteins that binds to an unstable conformer of another protein and stabilizes it. Chaperones prevent incorrect interaction between non-native polypeptides which increases the yield but not the rate of reaction. The Bcl-2-associated athanogene (BAG) is a multifunctional group of proteins belonging to BAG family of co-chaperones. Recent studies demonstrates that chaperones interact with PD-related proteins. Co-chaperones like BAG family proteins regulate the function of chaperones. Molecular chaperones regulate the mitochondrial functions by interacting with the PD-related proteins associated with it. This review studies the contribution of chaperones and PD-related proteins in pathogenesis of PD aiming to provide an alternate molecular target for preventing the disease progression.
摘要:
帕金森病(PD)是一种慢性快速增长的中枢神经系统(CNS)神经退行性疾病,其特征是黑质致密部(SNpc)中多巴胺能神经元的进行性丧失和路易体(LBs)的形成,导致基底神经节内多巴胺缺乏,导致运动和非运动表现。据报道,许多因素导致PD的发病,其中包括环境因素,遗传因素,和衰老因素。而多巴胺能神经元的死亡也是由氧化应激引起的,神经炎症,和自噬障碍。分子伴侣/共伴侣是与另一种蛋白质的不稳定构象体结合并使其稳定的蛋白质。分子伴侣防止非天然多肽之间的不正确相互作用,这增加了产率但不增加反应速率。Bcl-2相关基因(BAG)是一组多功能蛋白,属于BAG共同伴侣家族。最近的研究表明,伴侣与PD相关蛋白相互作用。如BAG家族蛋白的共同伴侣调节伴侣的功能。分子伴侣通过与PD相关蛋白相互作用来调节线粒体功能。本文综述了分子伴侣和PD相关蛋白在PD发病机制中的作用,旨在为预防疾病进展提供替代的分子靶标。