热休克蛋白对帕金森病患者的神经保护作用

Neuroprotective role of heat shock proteins in patients with Parkinson disease

目的:阐述机体在应激条件下迅速合成的一组蛋白质-热休克蛋白与帕金森病的关系,对热休克蛋白神经保护作用的可能机制进行剖析。资料来源:应用计算机检索Pubmed数据库1990-01/2005-10关于热休克蛋白对帕金森病神经保护功能的相关文章,检索词“Heatshockproteins”和“Parkinson’sdisease,neurodegenerativedisease,α-synuclein”分别组合进行检索,限定文章语言种类为English。同时计算机检索中国期刊全文数据库1995-01/2005-10关于热休克蛋白对帕金森病神经保护功能的相关文章,检索词“热休克蛋白,帕金森病,神经退行性疾病,α-突触核蛋白”,限定文章语言种类为中文。资料选择:对资料进行初审,从查到的资料中选取有关热休克蛋白神经保护作用的文章。纳入标准:①随机对照临床和基础研究,采用单盲、双盲或非盲法。②实验包含平行对照组。排除标准:重复性研究。资料提炼:共收集到446篇关于热休克蛋白神经保护作用的文章,入选16篇,入选的文章能包含其他文章的内容,体现了热休克蛋白对帕金森病保护作用的研究进展。排除的430篇为非随机对照研究或重复性研究。资料综合:①近期研究表明热休克蛋白在帕金森病中表达并有神经保护作用,而这一保护作用与α-突触核蛋白密切相关。热休克本身并不会降低α-突触核蛋白的表达水平,由热休克诱导产生的一种保护性蛋白质对α-突触核蛋白所导致的凋亡起到抑制作用。②直接用过表达热休克蛋白70基因的模型来研究应激蛋白的神经保护作用发现,无论是在体内还是体外,分子伴侣热休克蛋白70都能够减少α-突触核蛋白错误折叠和聚集的量,并且对由α-突触核蛋白聚集所致的细胞毒性起抵抗作用。③小分子热休克蛋白的功能之一是在生理应激条件和神经系统疾病时调节蛋白结构。帕金森病患者病变区附近的星形胶质细胞和小胶质细胞中都有小分子热休克蛋白如热休克蛋白-27和αB-晶状体球蛋白表达。热休克蛋白在神经退行性病变过程中也是充当保护性的角色。结论:帕金森病患者的神经细胞中有热休克蛋白的表达,并且该蛋白具有神经保护作用。其可能机制主要集中在热休克蛋白减少α-突触核蛋白的聚集和毒性以及减少细胞的凋亡和坏死上。

OBJECTIVE： To explain the relationship between heat shock proteins （a series proteins rapidly synthetized under stress） and Parkinson disease, and analyze the possible mechanism of the neuroprotective effect of heat shock proteins. DATA SOURCES： A computer-based online search of Pubmed database was undertaken to identify articles about the neuroprotective effect of heat shock proteins on Parkinson disease published in English between January 1990 and October 2005 by using the keywords of ＂heat shock proteins, Parkinson disease, neurodegenerative disease, α-synuclein＂. Meanwhile, Chinese articles about the neuroprotective effect of heat shock proteins on Parklnson disease published between January 1995 and October 2005 were searched in Chinese journal full-text database with the stone keywords in Chinese. STUDY SELECTION： All articles were selected firstly, those relevant to the neuroprotective role of heat shock proteins were selected, Inclusive criteria： （1）Randomized control clinical and basic researches, single blind, double blind or non-blind trials; 2） Experiments including parallel-control group. Exclusive criteria： duplicated researches. DATA EXTRACTION： Totally 466 articles about the neuroprotective role of heat shock proteins were collected, 16 were enrolled. The enrolled articles contained the contents of other articles and reflected the progress of the research on the neuroprotective role of heat shock proteins in Parkinson disease. The excluded 430 articles were non-randomized control study or duplicated researches. DATA SYNTHESIS： （1） Recent studies indicated that heat shock proteins expressed in Parkinson disease and had the neuroprotective effect, which was closely correlated with α-synuclein. Heat shock protein itself could not decrease the expression of α-synuclein, a kind of pratective protein induced by heat shock proteins could inhibit the apoptosis caused by α-synuclein. （2） The study about the neuroprotective effect of heat shock proteins by directly using the model of overexpressed heat shock protein-70 gene found that, no matter in vivo or in vitro, the molecular chaperone of heat shock protein270 could reduce the mistake folding and aggregation of α-synuclein, and could resist the cytotoxicity induced by the aggregation of α-synuclein. （3） One of the functions of small molecular heat shock protein is to adjust protein structure under physiological condition and disease of nervous system. There were expressions of small molecular heat shock proteins, such as heat shock protein-27 and a B-crystalline lens globulin in astrocytes and microglia around the lesion area of patients with Parkinson disease. Heat shock proteins also play a protective role in the process of neurodcgenerative disease. CONCLUSION： Heat shock proteins expressed in the neurons of patients with Parkinson disease and had the neuroprotective function. The possible mechanism mainly concentrates on the reduces of aggregation and toxicity of α-synuclein by heat shock proteins, also the decreases of apoptosis and necrosis.