The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson's Disease.
The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson's Disease.
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帕金森病中内质网应激、自噬和神经变性的交联
DOI：
10.3389/fnagi.2021.691881
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发表时间：
2021
影响因子：
4.8
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Ren H;Zhai W;Lu X;Wang G
帕金森病（Parkinson's disease，PD）是最常见的神经退行性运动障碍，其特征是黑质（substantia nigra pars arteriota，SNpc）多巴胺能（dopaminergic，DA）神经元的选择性丢失，以及存活的DA神经元中存在以α-突触核蛋白为主要成分的细胞内包涵体。新的证据表明，蛋白质稳态失衡是PD的一个关键致病因素。内质网应激诱导的未折叠蛋白反应（UPR）和自噬是维持蛋白质稳态的两条主要途径，在PD病理过程中起重要作用，被认为是PD治疗的重要靶点。然而，尽管ER应激/UPR和自噬似乎是独立的细胞过程，但它们彼此密切相关。本文就ER应激/UPR与自噬在PD病理中的作用及其分子交联进行综述。本文对ER应激/UPR和自噬的调控及其交联机制的最新研究进展进行了系统的综述。我们还回顾和讨论了ER应激/UPR激活和自噬失调在PD患者病变区域共存的机制，以及ER应激/UPR激活和自噬失调在PD相关遗传因子和PD相关神经毒素诱导的DA神经变性中的潜在作用和分子交联。最后，我们指出，ER应激/UPR和自噬的联合调节将是PD的更有效的治疗方法，而不是单独调节这些条件之一。
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, and it is characterized by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), as well as the presence of intracellular inclusions with α-synuclein as the main component in surviving DA neurons. Emerging evidence suggests that the imbalance of proteostasis is a key pathogenic factor for PD. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and autophagy, two major pathways for maintaining proteostasis, play important roles in PD pathology and are considered as attractive therapeutic targets for PD treatment. However, although ER stress/UPR and autophagy appear to be independent cellular processes, they are closely related to each other. In this review, we focused on the roles and molecular cross-links between ER stress/UPR and autophagy in PD pathology. We systematically reviewed and summarized the most recent advances in regulation of ER stress/UPR and autophagy, and their cross-linking mechanisms. We also reviewed and discussed the mechanisms of the coexisting ER stress/UPR activation and dysregulated autophagy in the lesion regions of PD patients, and the underlying roles and molecular crosslinks between ER stress/UPR activation and the dysregulated autophagy in DA neurodegeneration induced by PD-associated genetic factors and PD-related neurotoxins. Finally, we indicate that the combined regulation of ER stress/UPR and autophagy would be a more effective treatment for PD rather than regulating one of these conditions alone.
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影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
--
作者：
Alvarez-Erviti, Lydia;Rodriguez-Oroz, Maria C.;Schapira, Anthony H. V.
通讯作者：
Schapira, Anthony H. V.
影响因子：
6.6
作者：
Bruening, Ansgar;Rahmeh, Martina;Friese, Klaus
通讯作者：
Friese, Klaus
影响因子：
5.1
作者：
Coppola-Segovia, Valentin;Cavarsan, Clarissa;Zanata, Silvio M.
通讯作者：
Zanata, Silvio M.
DOI：
10.1523/jneurosci.5367-11.2012
发表时间：
2012-03-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Colla E;Coune P;Liu Y;Pletnikova O;Troncoso JC;Iwatsubo T;Schneider BL;Lee MK
通讯作者：
Lee MK