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热休克蛋白与帕金森病中 parkin/α-突触核蛋白轴的关系。

Involvement of heat shock proteins and parkin/α-synuclein axis in Parkinson's disease.

机构信息

Department of biology, Islamic Azad University, Tabriz, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Mol Biol Rep. 2022 Nov;49(11):11061-11070. doi: 10.1007/s11033-022-07900-5. Epub 2022 Sep 12.

Abstract

Parkinson's disease (PD) is one of the most common neurological diseases, next only to Alzheimer's disease (AD) in terms of prevalence. It afflicts about 2-3% of individuals over 65 years old. The etiology of PD is unknown and several environmental and genetic factors are involved. From a pathological point of view, PD is characterized by the loss of dopaminergic neurons in the substantia nigra, which causes the abnormal accumulation of α-synuclein (α-syn) (a component of Lewy bodies), which subsequently interact with heat shock proteins (HSPs), leading to apoptosis. Apoptosis is a vital pathway for establishing homeostasis in body tissues, which is regulated by pro-apoptotic and anti-apoptotic factors. Recent findings have shown that HSPs, especially HSP27 and HSP70, play a pivotal role in regulating apoptosis by influencing the factors involved in the apoptosis pathway. Moreover, it has been reported that the expression of these HSPs in the nervous system is high. Apart from this finding, investigations have suggested that HSP27 and HSP70 (related to parkin) show a potent protective and anti-apoptotic impact against the damaging outcomes of mutant α-syn toxicity to nerve cells. Therefore, in this study, we aimed to investigate the relationship between these HSPs and apoptosis in patients with PD.

摘要

帕金森病(PD)是最常见的神经退行性疾病之一,仅次于阿尔茨海默病(AD)。它影响着大约 2-3%的 65 岁以上的人群。PD 的病因尚不清楚,涉及几个环境和遗传因素。从病理学角度来看,PD 的特征是黑质多巴胺能神经元的丧失,导致α-突触核蛋白(α-syn)(路易体的组成部分)的异常积累,随后与热休克蛋白(HSPs)相互作用,导致细胞凋亡。细胞凋亡是机体组织建立内稳态的重要途径,受促凋亡和抗凋亡因子的调节。最近的研究发现,热休克蛋白(HSPs),特别是 HSP27 和 HSP70,通过影响凋亡途径中涉及的因素,在调节凋亡中发挥关键作用。此外,据报道,这些 HSPs 在神经系统中的表达水平较高。除了这一发现,研究还表明,HSP27 和 HSP70(与 parkin 相关)对突变的α-syn 毒性对神经细胞的损伤具有强大的保护和抗凋亡作用。因此,在本研究中,我们旨在研究这些 HSPs 与 PD 患者细胞凋亡之间的关系。

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