Deconvoluting the complexity of autophagy and Parkinson's disease for potential therapeutic purpose.
Deconvoluting the complexity of autophagy and Parkinson's disease for potential therapeutic purpose.
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解开自噬和帕金森病的复杂性以实现潜在的治疗目的
DOI：
10.18632/oncotarget.5803
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Liu B
中科院分区：
文献类型：
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作者：
Li J;Li S;Zhang L;Ouyang L;Liu B
帕金森病（PD）是一种神经退行性疾病，其特征为多巴胺能神经元的选择性死亡。在过去二十年里，我们对帕金森病发病机制的认识取得了巨大进展；然而，其确切发病机制仍不明确。最近，越来越多的证据表明，巨自噬（本文简称为自噬）与帕金森病密切相关。在帕金森病患者的大脑以及帕金森病动物模型中，均观察到自噬通路的失调。更重要的是，多项研究进一步揭示，一些与帕金森病相关的蛋白，如α - 突触核蛋白、富亮氨酸重复激酶2（LRRK2）、帕金蛋白（Parkin）和PTEN诱导激酶1（PINK1），均参与了自噬过程。因此，目前人们认识到，持续性自噬对神经元存活至关重要，自噬失调会引发帕金森病。在这篇综述中，我们重点总结帕金森病相关蛋白、自噬与帕金森病之间的关系。此外，我们还阐述了帕金森病模型中一些调节自噬的化合物以及自噬相关的微小核糖核酸（miRNA），这可能为帕金森病的潜在治疗提供更有前景的策略。
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the preferential death of dopaminergic neurons. In the past two decades, great progress has been made toward understanding the pathogenesis of PD; however, its precise pathogenesis still remains unclear. Recently, accumulating evidence has suggested that macroautophagy (herein referred to as autophagy) is tightly linked to PD. Dysregulation of autophagic pathways has been observed in the brains of PD patients and in animal models of PD. More importantly, a number of PD-associated proteins, such as α-synuclein, LRRK2, Parkin and PINK1 have been further revealed to be involved in autophagy. Thus, it is now acknowledged that constitutive autophagy is essential for neuronal survival and that dysregulation of autophagy leads to PD. In this review, we focus on summarizing the relationships amongst PD-associated proteins, autophagy and PD. Moreover, we also demonstrate some autophagy-modulating compounds and autophagic microRNAs in PD models, which may provide better promising strategies for potential PD therapy.