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转录因子NRF2对蛋白质稳态的调节及其在神经退行性疾病中的影响

Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases.

作者信息

Pajares Marta, Cuadrado Antonio, Rojo Ana I

机构信息

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC, Madrid, Spain; Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC, Madrid, Spain; Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.

出版信息

Redox Biol. 2017 Apr;11:543-553. doi: 10.1016/j.redox.2017.01.006. Epub 2017 Jan 10.

DOI:10.1016/j.redox.2017.01.006
PMID:28104575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5239825/
Abstract

Neurodegenerative diseases are linked to the accumulation of specific protein aggregates, suggesting an intimate connection between injured brain and loss of proteostasis. Proteostasis refers to all the processes by which cells control the abundance and folding of the proteome thanks to a wide network that integrates the regulation of signaling pathways, gene expression and protein degradation systems. This review attempts to summarize the most relevant findings about the transcriptional modulation of proteostasis exerted by the transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2). NRF2 has been classically considered as the master regulator of the antioxidant cell response, although it is currently emerging as a key component of the transduction machinery to maintain proteostasis. As we will discuss, NRF2 could be envisioned as a hub that compiles emergency signals derived from misfolded protein accumulation in order to build a coordinated and perdurable transcriptional response. This is achieved by functions of NRF2 related to the control of genes involved in the maintenance of the endoplasmic reticulum physiology, the proteasome and autophagy.

摘要

神经退行性疾病与特定蛋白质聚集体的积累有关，这表明受损大脑与蛋白质稳态丧失之间存在密切联系。蛋白质稳态是指细胞通过一个广泛的网络来控制蛋白质组的丰度和折叠的所有过程，该网络整合了信号通路、基因表达和蛋白质降解系统的调控。本综述试图总结转录因子NRF2（核因子（红系衍生2）样2）对蛋白质稳态进行转录调控的最相关研究结果。NRF2传统上被认为是抗氧化细胞反应的主要调节因子，尽管它目前正成为维持蛋白质稳态的转导机制的关键组成部分。正如我们将讨论的，NRF2可以被设想为一个枢纽，它整合了来自错误折叠蛋白质积累的紧急信号，以便建立协调且持久的转录反应。这是通过NRF2与控制参与内质网生理、蛋白酶体和自噬维持的基因相关的功能来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/5239825/70e3f6d60791/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/5239825/645286dfb67f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/5239825/8abaa0b2c21b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/5239825/010fcb65db41/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/5239825/70e3f6d60791/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/5239825/645286dfb67f/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/5239825/8abaa0b2c21b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/5239825/010fcb65db41/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea71/5239825/70e3f6d60791/gr4.jpg

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