Department of Biochemistry, Weill Cornell Medical College in Qatar, Qatar Foundation, Education City, Doha, Qatar.
Int J Biol Macromol. 2013 Sep;60:196-205. doi: 10.1016/j.ijbiomac.2013.05.032. Epub 2013 Jun 5.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the accumulation of a protein called α-synuclein (α-syn) into inclusions known as lewy bodies (LB) within neurons. This accumulation is also due to insufficient formation and activity of dopamine produced in certain neurons within the substantia nigra. Lewy bodies are the pathological hallmark of the idiopathic disorder and the cascade that allows α-synuclein to misfold, aggregate and form these inclusions has been the subject of intensive research. Targeting these early steps of oligomerization is one of the main therapeutic approaches in order to develop neurodegenerative-modifying agents. Because the folding and refolding of alpha synuclein is the key point of this cascade, we are interested in this review to summarize the role of some molecular chaperones proteins such as Hsp70, Hsp90 and small heat shock proteins (sHsp) and Hsp 104. Hsp70 and its co-chaperone, Hsp70 and small heat shock proteins can prevent neurodegeneration by preventing α-syn misfolding, oligomerization and aggregation in vitro and in Parkinson disease animal models. Hsp104 is able to resolve disordered protein aggregates and cross beta amyloid conformers. Together, these chaperones have a complementary effect and can be a target for therapeutic intervention in PD.
帕金森病(PD)是一种神经退行性疾病,其特征是一种称为α-突触核蛋白(α-syn)的蛋白质在神经元内积累成称为路易体(LB)的包涵体。这种积累还归因于黑质内某些神经元中产生的多巴胺的形成和活性不足。路易体是特发性疾病的病理标志,允许α-突触核蛋白错误折叠、聚集并形成这些包涵体的级联反应一直是密集研究的主题。针对寡聚化的这些早期步骤是开发神经退行性变修饰剂的主要治疗方法之一。由于α-突触核蛋白的折叠和重折叠是该级联反应的关键点,我们有兴趣在这篇综述中总结一些分子伴侣蛋白的作用,如 Hsp70、Hsp90 和小热休克蛋白(sHsp)和 Hsp104。Hsp70 及其共伴侣 Hsp70 和小热休克蛋白可以通过防止 α-syn 在体外和帕金森病动物模型中错误折叠、寡聚化和聚集来预防神经退行性变。Hsp104 能够解决无序的蛋白质聚集体和交叉β淀粉样蛋白构象。这些伴侣蛋白共同具有互补作用,可能成为 PD 治疗干预的靶点。