Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Autophagy and neurodegeneration
Rebecca A. Frake, … , Fiona M. Menzies, David C. Rubinsztein
Rebecca A. Frake, … , Fiona M. Menzies, David C. Rubinsztein
Published January 2, 2015
Citation Information: J Clin Invest. 2015;125(1):65-74. https://doi.org/10.1172/JCI73944.
View: Text | PDF
Review

Autophagy and neurodegeneration

  • Text
  • PDF
Abstract

Most neurodegenerative diseases that afflict humans are associated with the intracytoplasmic deposition of aggregate-prone proteins in neurons. Autophagy is a powerful process for removing such proteins. In this Review, we consider how certain neurodegenerative diseases may be associated with impaired autophagy and how this may affect pathology. We also discuss how autophagy induction may be a plausible therapeutic strategy for some conditions and review studies in various models that support this hypothesis. Finally, we briefly describe some of the signaling pathways that may be amenable to therapeutic targeting for these goals.

Authors

Rebecca A. Frake, Thomas Ricketts, Fiona M. Menzies, David C. Rubinsztein

×

Figure 2

Points of action of autophagy-upregulating agents.

Options: View larger image (or click on image) Download as PowerPoint
Points of action of autophagy-upregulating agents.
This simplified schem...
This simplified schematic shows some of the pathways known to control autophagy and indicates where drugs and other agents act that are used to upregulate autophagy. In the interest of clarity, not all interactions of these pathways are shown. Both the mTOR-dependent and mTOR-independent pathways negatively regulate the autophagic process, and inhibition of these pathways will lead to an upregulation of autophagy. In the case of mTOR, this may occur through relieving the inhibition of the ULK1 complex, which is a positive regulator of autophagy. In the case of mTOR-independent regulation, the points of interaction between many agents in this category and the autophagy machinery are not known.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts