The different autophagy degradation pathways and neurodegeneration

被引：306

作者：

Fleming, Angeleen ^{[1
,2
,3
]}

Bourdenx, Mathieu ^{[4
,5
]}

Fujimaki, Motoki ^{[1
,2
]}

Karabiyik, Cansu ^{[1
,2
]}

Krause, Gregory J. ^{[6
,7
]}

Lopez, Ana ^{[1
,2
,3
]}

Martin-Segura, Adrian ^{[6
,7
]}

Puri, Claudia ^{[1
,2
]}

Scrivo, Aurora ^{[6
,7
]}

Skidmore, John ^{[8
]}

Son, Sung Min ^{[1
,2
]}

Stamatakou, Eleanna ^{[1
,2
]}

Wrobel, Lidia ^{[1
,2
]}

Zhu, Ye ^{[1
,2
]}

Cuervo, Ana Maria ^{[6
,7
]}

Rubinsztein, David C. ^{[1
,2
]}

机构：

[1] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Keith Peters Bldg,Cambridge Biomed Campus, Cambridge CB2 0XY, England

[2] Univ Cambridge, UK Dementia Res Inst, Cambridge Inst Med Res, Keith Peters Bldg,Cambridge Biomed Campus, Cambridge CB2 0XY, England

[3] Univ Cambridge, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3DY, England

[4] Univ Bordeaux, Inst Malad Neurodegenerat, UMR 5293, F-33000 Bordeaux, France

[5] CNRS, UMR 5293, Inst Malad Neurodegenerat, F-33000 Bordeaux, France

[6] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA

[7] Albert Einstein Coll Med, Inst Aging Studies, Bronx, NY 10467 USA

[8] Univ Cambridge, ALBORADA Drug Discovery Inst, Isl Res Bldg,Cambridge Biomed Campus,Hills Rd, Cambridge CB2 0AH, England

来源：

NEURON | 2022年 / 110卷 / 06期

基金：

美国国家卫生研究院;

关键词：

CHAPERONE-MEDIATED AUTOPHAGY; ENDOPLASMIC-RETICULUM TURNOVER; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; MUTANT HUNTINGTIN; MOUSE MODEL; DEFECTIVE AUTOPHAGY; SELECTIVE AUTOPHAGY; SEQUESTOSOME; 1/P62; DOPAMINE NEURONS;

D O I：

10.1016/j.neuron.2022.01.017

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 auto-phagic 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.

引用

页码：935 / 966

页数：32

共 328 条

[41] Microglia clear neuron-released a-synuclein via selective autophagy and prevent neurodegeneration [J].