The different autophagy degradation pathways and neurodegeneration.


Type
Article
Change log
Authors
Bourdenx, Mathieu 
Fujimaki, Motoki 
Karabiyik, Cansu 
Krause, Gregory J 
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.

Description
Keywords
Apoptosis, Autophagy, Brain, Humans, Lysosomes, Neurons
Journal Title
Neuron
Conference Name
Journal ISSN
0896-6273
1097-4199
Volume Title
Publisher
Elsevier BV
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (RG50822)
Alzheimer's Research UK (ARUK-PG2018C-001)
Alzheimer's Research UK (ARUK-2021DDI-CAM)
National Institute for Health and Care Research (IS-BRC-1215-20014)
This work was supported by UK Dementia Research Institute (funded by the MRC, Alzheimer's Research UK and the Alzheimer's Society), Alzheimer's Research UK (ARUK-2022DDI-CAM, ARUK-TC2020-1 and ARUK-PG2018C-001), The Tau Consortium, Cambridge Centre for Parkinson-Plus, the National Institutes of Health grants AG054108, AG031782, AG021904, NS100717 and the generous support of the Rainwater Charitable Foundation, The JPB Foundation, The Backus Foundation, The Glenn Foundation and R&R Belfer and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care'. AMS is supported by a Ramon Areces postdoctoral fellowship and GJK by a T32 GM007491 and a T32 GM007288. MB is supported by an ‘Allocation Jeune Chercheur’ from Fondation Alzheimer (France).