The Role of PERK in Understanding Development of Neurodegenerative Diseases.

The Role of PERK in Understanding Development of Neurodegenerative Diseases.
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PERK在了解神经退行性疾病发展中的作用。

DOI:
10.3390/ijms22158146
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发表时间:
2021-07-29
影响因子:
5.6
通讯作者:
Yuan SH
Yuan SH
中科院分区:
生物学2区
文献类型:
--
作者:
Smedley GD;Walker KE;Yuan SH

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神经退行性疾病是快速老龄化人口日益严重的问题。尽管如此,我们对这些神经退行性疾病如何发展和进展的理解,在大多数情况下是初步的。蛋白激酶RNA (PKR)样ER激酶(PERK)包括细胞试图管理细胞应激的三种未折叠蛋白反应途径之一。然而,由于其在细胞应激反应中的作用以及该途径的深远影响,PERK途径中的错误已被证明可导致各种病理。遗传和临床研究表明,神经细胞中PERK通路的失效与神经退行性变的发展之间存在相关性,但这些研究的各种方法对PERK在这些受影响系统中的作用提出了相互矛盾的说法。由于PERK与病理之间的联系,PERK已成为了解神经退行性疾病和潜在治疗方法的高价值研究目标。在这里,我们回顾了PubMed检索到的PERK通路的文献,以及研究该蛋白在神经退行性疾病发展中的作用以及它如何作为治疗靶点所涉及的一些复杂性。
Neurodegenerative diseases are an ever-increasing problem for the rapidly aging population. Despite this, our understanding of how these neurodegenerative diseases develop and progress, is in most cases, rudimentary. Protein kinase RNA (PKR)-like ER kinase (PERK) comprises one of three unfolded protein response pathways in which cells attempt to manage cellular stress. However, because of its role in the cellular stress response and the far-reaching implications of this pathway, error within the PERK pathway has been shown to lead to a variety of pathologies. Genetic and clinical studies show a correlation between failure of the PERK pathway in neural cells and the development of neurodegeneration, but the wide array of methodology of these studies is presenting conflicting narratives about the role of PERK in these affected systems. Because of the connection between PERK and pathology, PERK has become a high value target of study for understanding neurodegenerative diseases and potentially how to treat them. Here, we present a review of the literature indexed in PubMed of the PERK pathway and some of the complexities involved in investigating the protein’s role in the development of neurodegenerative diseases as well as how it may act as a target for therapeutics.
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