The different autophagy degradation pathways and neurodegeneration

Angeleen Fleming, Mathieu Bourdenx, Motoki Fujimaki, Cansu Karabiyik, Gregory J. Krause, Ana Lopez, Adrián Martín-Segura, Claudia Puri, Aurora Scrivo, John Skidmore, Sung Min Son, Eleanna Stamatakou, Lidia Wrobel, Ye Zhu, Ana Maria Cuervo, David C. Rubinsztein

Research output: Contribution to journalReview articlepeer-review

85 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)935-966
Number of pages32
Issue number6
StatePublished - Mar 16 2022

ASJC Scopus subject areas

  • Neuroscience(all)


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