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未折叠蛋白反应在衰老驱动的神经退行性疾病中的纠缠。

Entanglement of UPR in Aging Driven Neurodegenerative Diseases.

作者信息

Rahman Safikur, Jan Arif Tasleem, Ayyagari Archana, Kim Jiwoo, Kim Jihoe, Minakshi Rinki

机构信息

Department of Medical Biotechnology, Yeungnam University, Gyeongsan, South Korea.

Department of Microbiology, Swami Shraddhanand College, University of Delhi, New Delhi, India.

出版信息

Front Aging Neurosci. 2017 Oct 24;9:341. doi: 10.3389/fnagi.2017.00341. eCollection 2017.

Abstract

The endoplasmic reticulum (ER) is an indispensable cellular organelle that remains highly active in neuronal cells. The ER bears the load of maintaining protein homeostasis in the cellular network by managing the folding of incoming nascent peptides; however, the stress imposed by physiological/environmental factors can cause ER dysfunctions that lead to the activation of ER unfolded protein response (UPR). Aging leads to deterioration of several cellular pathways and therefore weakening of the UPR. The decline in functioning of the UPR during aging results in accumulation of misfolded proteins that becomes intracellular inclusions in neuronal cells, resulting in toxicity manifested as neurodegenerative diseases. With ascension in cases of neurodegenerative diseases, understanding the enigma behind aging driven UPR dysfunction may lead to possible treatments.

摘要

内质网(ER)是一种不可或缺的细胞器,在神经元细胞中保持高度活跃。内质网通过管理新生肽的折叠来承担维持细胞网络中蛋白质稳态的重任;然而,生理/环境因素施加的压力会导致内质网功能障碍,进而引发内质网未折叠蛋白反应(UPR)的激活。衰老会导致多种细胞通路的退化,从而削弱UPR。衰老过程中UPR功能的下降会导致错误折叠蛋白的积累,这些蛋白在神经元细胞中形成细胞内包涵体,导致以神经退行性疾病形式表现出来的毒性。随着神经退行性疾病病例的增加,了解衰老驱动的UPR功能障碍背后的谜团可能会带来潜在的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0122/5660724/89b57f914b39/fnagi-09-00341-g0001.jpg

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