TY - JOUR
T1 - The different autophagy degradation pathways and neurodegeneration
AU - Fleming, Angeleen
AU - Bourdenx, Mathieu
AU - Fujimaki, Motoki
AU - Karabiyik, Cansu
AU - Krause, Gregory J.
AU - Lopez, Ana
AU - Martín-Segura, Adrián
AU - Puri, Claudia
AU - Scrivo, Aurora
AU - Skidmore, John
AU - Son, Sung Min
AU - Stamatakou, Eleanna
AU - Wrobel, Lidia
AU - Zhu, Ye
AU - Cuervo, Ana Maria
AU - Rubinsztein, David C.
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/3/16
Y1 - 2022/3/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2022.01.017
DO - 10.1016/j.neuron.2022.01.017
M3 - Review article
C2 - 35134347
AN - SCOPUS:85126281939
SN - 0896-6273
VL - 110
SP - 935
EP - 966
JO - Neuron
JF - Neuron
IS - 6
ER -