摘要
未折叠蛋白反应(UPR)在维持细胞稳态作为内质网(ER)应激的结果起着至关重要的作用。然而,长期的未折叠蛋白反应的活动导致细胞死亡。这种随时间变化的双重功能的未折叠蛋白反应适应性和细胞毒途径起因于内质网应激。慢性未折叠蛋白反应激活全身和神经退行性疾病已被确定为细胞稳态失衡的早期征兆。 蛋白质激酶类似内质网激酶(PERK)途径是未折叠蛋白元件三大分支之一,它是唯一一个调节蛋白质合成是一种适应性反应。长期活跃活动的特定识别相关的进展的疾病如糖尿病,阿尔茨海默症和癌症,表明活跃在这些疾病的病理过程中发挥作用。第一次,“PERK-opathies”一词用于这些疾病在活跃介导损害细胞在慢性疾病。本文综述文献记录系统性疾病之间的联系与未折叠蛋白反应,但特别强调活跃通路。然后,文章报告呈现了未折叠蛋白反应之间,尤其是类似内质网激酶以及神经退行性疾病的联系。最后,从治疗的角度进行了讨论,类似内质网激酶的干预可能是慢性神经退行性疾病的细胞功能障碍的潜在的补救措施。
关键词: eIF2α
Current Alzheimer Research
Title:PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration
Volume: 13 Issue: 2
Author(s): Michelle C. Bell, Shelby E. Meier, Alexandria L. Ingram and Jose F. Abisambra
Affiliation:
关键词: eIF2α
摘要: The unfolded protein response (UPR) plays a vital role in maintaining cell homeostasis as a consequence of endoplasmic reticulum (ER) stress. However, prolonged UPR activity leads to cell death. This time-dependent dual functionality of the UPR represents the adaptive and cytotoxic pathways that result from ER stress. Chronic UPR activation in systemic and neurodegenerative diseases has been identified as an early sign of cellular dyshomeostasis.
The Protein Kinase R-like ER Kinase (PERK) pathway is one of three major branches in the UPR, and it is the only one to modulate protein synthesis as an adaptive response. The specific identification of prolonged PERK activity has been correlated with the progression of disorders such as diabetes, Alzheimer’s disease, and cancer, suggesting that PERK plays a role in the pathology of these disorders. For the first time, the term “PERK-opathies” is used to group these diseases in which PERK mediates detriment to the cell culminating in chronic disorders. This article reviews the literature documenting links between systemic disorders with the UPR, but with a specific emphasis on the PERK pathway. Then, articles reporting links between the UPR, and more specifically PERK, and neurodegenerative disorders are presented. Finally, a therapeutic perspective is discussed, where PERK interventions could be potential remedies for cellular dysfunction in chronic neurodegenerative disorders.
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Michelle C. Bell, Shelby E. Meier, Alexandria L. Ingram and Jose F. Abisambra , PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration, Current Alzheimer Research 2016; 13 (2) . https://dx.doi.org/10.2174/1567205013666151218145431
DOI https://dx.doi.org/10.2174/1567205013666151218145431 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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