Cited by 435Autophagy in Disease and TherapyAlzheimer's disease research and treatmentsCalcium signaling and nucleotide metabolism

The DOI matches its Crossref record; 319 of the 319 references it cites were found in a registry or an index.

Mechanisms of autophagy–lysosome dysfunction in neurodegenerative diseases

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Nixon, Ralph A., Rubinsztein, David C.·2024·Nature Reviews Molecular Cell Biology

Abstract

Autophagy is a lysosome-based degradative process used to recycle obsolete cellular constituents and eliminate damaged organelles and aggregate-prone proteins. Their postmitotic nature and extremely polarized morphologies make neurons particularly vulnerable to disruptions caused by autophagy-lysosomal defects, especially as the brain ages. Consequently, mutations in genes regulating autophagy and lysosomal functions cause a wide range of neurodegenerative diseases. Here, we review the role of autophagy and lysosomes in neurodegenerative diseases such as Alzheimer disease, Parkinson disease and frontotemporal dementia. We also consider the strong impact of cellular ageing on lysosomes and autophagy as a tipping point for the late-age emergence of related neurodegenerative disorders. Many of these diseases have primary defects in autophagy, for example affecting autophagosome formation, and in lysosomal functions, especially pH regulation and calcium homeostasis. We have aimed to provide an integrative framework for understanding the central importance of autophagic-lysosomal function in neuronal health and disease.

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Research works printed but not linked: 3

  1. Lees, M. B. Basic Neurochemistry 5th edn, Vol. 39 (Raven Press, 1994).
  2. de Duve, C. Lysosomes, a New Group of Cytoplasmic Particle (Ronald Press, 1959).
  3. Chou, C. C. et al. Proteostasis and lysosomal quality control deficits in Alzheimer’s disease neurons. Preprint at bioRxiv https://doi.org/10.1101/2023.03.27.534444 (2023). · DOI

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Metadata

Authors
Nixon, R. A., & Rubinsztein, D. C.
Affiliations
  • Nathan Kline Institute for Psychiatric Research (US)
  • University of Cambridge (GB)
Corresponding author
Nixon, Ralph A.
Venue
Nature Reviews Molecular Cell Biology
Published
2024-08-06
Volume
25
Issue
11
Pages
926-946
ISSN
  • 1471-0072 (ISSN-L)
  • 1471-0080
OpenAlex
W4401363901
Cited by
435
References
319
Citations by year
2026: 260 · 2025: 160 · 2024: 14
FWCI
26.31
Type
journal article
Language
en
Open access
Locations
  • Nature Reviews Molecular Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • CHDI Foundation
  • Rainwater Charitable Foundation
  • Alzheimer's Society
  • National Institute for Health and Care Research ((NIHR203312)
  • Department of Health and Social Care
  • Parkinson's UK
  • Rosetrees Trust
  • UK Dementia Research Institute
  • Medical Research Council (NIHR203312)
  • NIHR Cambridge Biomedical Research Centre (NIHR 203312)
  • National Institute on Aging (P01AG017617, R01AG062376)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
autophagy, lysosomes, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, neuronal aging, autophagosome formation, calcium homeostasis, protein aggregate clearance, lysosomal storage disease
MeSH terms
Autophagosomes, Animals, Autophagy, Humans, Lysosomes, Neurons, Neurodegenerative Diseases

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