National Centre for Cell Science, Savitribai Phule Pune University, Pune, India.
FEBS J. 2019 Jul;286(13):2447-2460. doi: 10.1111/febs.14826. Epub 2019 Apr 4.
Autophagy is a constitutive and cytoprotective catabolic process. Aberrations in autophagy lead to a multitude of degenerative disorders, with neurodegeneration being one of the most widely studied autophagy-related disorders. While the field has largely been focusing on the cytosolic constituents and processes of autophagy, recent studies are increasingly appreciating the role of chromatin modifications and epigenetic regulation in autophagy maintenance. Autophagy has been implicated in the regulation of neurogenesis, and disruption of neurogenesis in response to psychological stress is a proximal risk factor for development of neuropsychiatric disorders such as major depressive disorder (MDD). In this review, we will discuss the regulation of autophagy in normal neurogenesis as well as during chronic psychological stress, focusing on the epigenetic control of autophagy in these contexts, and also highlight the lacunae in our understanding of this process. The systematic study of these regulatory mechanisms will provide a novel therapeutic strategy, based on the use epigenetic regulators of autophagy to enhance neurogenesis and potentially alleviate stress-related behavioral disorders.
自噬是一种组成型的、具有细胞保护作用的分解代谢过程。自噬的异常会导致多种退行性疾病,神经退行性疾病是研究最多的与自噬相关的疾病之一。尽管该领域主要集中在自噬的细胞质成分和过程上,但最近的研究越来越重视染色质修饰和表观遗传调控在自噬维持中的作用。自噬被认为参与了神经发生的调节,而神经发生对心理应激的破坏是神经精神障碍(如重度抑郁症)发展的一个近端危险因素。在这篇综述中,我们将讨论自噬在正常神经发生以及慢性心理应激中的调节,重点讨论自噬在这些情况下的表观遗传调控,并强调我们对这一过程理解上的空白。对这些调节机制的系统研究将提供一种新的治疗策略,即基于使用自噬的表观遗传调节剂来增强神经发生,并可能缓解与应激相关的行为障碍。