Jones Daryl Rhys, Moussaud Simon, McLean Pamela
Mayo Clinic, Jacksonville, FL, USA.
Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Ther Adv Neurol Disord. 2014 Jan;7(1):33-51. doi: 10.1177/1756285613493469.
Parkinson's disease is a slowly progressive neurodegenerative disorder typically characterized by the loss of dopaminergic neurons within the substantia nigra pars compacta, and the intraneuronal deposition of insoluble protein aggregates chiefly comprised of α-synuclein. Patients experience debilitating symptoms including bradykinesia, rigidity and postural instability. No curative treatment currently exists and therapeutic strategies are restricted to symptomatic treatment only. Over the past decade a class of molecular chaperones called the heat shock proteins has emerged as a potentially promising therapeutic target. Heat shock proteins aid in the folding and refolding of proteins, and target denatured proteins to degradation systems. By targeting heat shock proteins through various means including overexpression and pharmacological enhancement, researchers have shown that α-synuclein aggregation and its associated cytotoxicity can be therapeutically modulated in an array of cell and animal models. This review highlights the relevant progress in this field and discusses the relevance of heat shock proteins as therapeutic modulators of α-synuclein toxicity to the rapidly evolving understanding of Parkinson's disease pathogenesis.
帕金森病是一种缓慢进展的神经退行性疾病，其典型特征是黑质致密部多巴胺能神经元的丧失，以及主要由α-突触核蛋白组成的不溶性蛋白质聚集体在神经元内沉积。患者会出现运动迟缓、僵硬和姿势不稳等使人衰弱的症状。目前尚无治愈性治疗方法，治疗策略仅限于对症治疗。在过去十年中，一类称为热休克蛋白的分子伴侣已成为一个潜在的有前景的治疗靶点。热休克蛋白有助于蛋白质的折叠和重新折叠，并将变性蛋白质靶向降解系统。通过包括过表达和药理学增强在内的各种手段靶向热休克蛋白，研究人员已表明，在一系列细胞和动物模型中，α-突触核蛋白聚集及其相关的细胞毒性可通过治疗进行调节。本综述强调了该领域的相关进展，并讨论了热休克蛋白作为α-突触核蛋白毒性的治疗调节剂与对帕金森病发病机制的快速发展的理解之间的相关性。
