학술논문

The different autophagy degradation pathways and neurodegeneration.
Document Type
Article
Source
Neuron. Mar2022, Vol. 110 Issue 6, p935-966. 32p.
Subject
*AUTOPHAGY
*APOPTOSIS
*NEURODEGENERATION
*PROTEOLYSIS
*CELL division
*LYSOSOMES
Language
ISSN
0896-6273
Abstract
The term autophagy encompasses different pathways that route cytoplasmic material to lysosomes for degradation and includes macroautophagy, chaperone-mediated autophagy, and microautophagy. Since these pathways are crucial for degradation of aggregate-prone proteins and dysfunctional organelles such as mitochondria, they help to maintain cellular homeostasis. As post-mitotic neurons cannot dilute unwanted protein and organelle accumulation by cell division, the nervous system is particularly dependent on autophagic pathways. This dependence may be a vulnerability as people age and these processes become less effective in the brain. Here, we will review how the different autophagic pathways may protect against neurodegeneration, giving examples of both polygenic and monogenic diseases. We have considered how autophagy may have roles in normal CNS functions and the relationships between these degradative pathways and different types of programmed cell death. Finally, we will provide an overview of recently described strategies for upregulating autophagic pathways for therapeutic purposes. The term autophagy encompasses different pathways enabling lysosomal degradation of cytoplasmic material, such as macroautophagy, chaperone-mediated autophagy, and microautophagy. Fleming et al. review how different autophagic pathways protect against neurodegeneration and consider recently described therapeutic strategies exploiting autophagic upregulation. [ABSTRACT FROM AUTHOR]