Autophagy and the ubiquitin-proteasome system: Collaborators in neuroprotection
Open accessAbstract
Protein degradation is an essential cellular function that, when dysregulated or impaired, can lead to a wide variety of disease states. The two major intracellular protein degradation systems are the ubiquitin-proteasome system (UPS) and autophagy, a catabolic process that involves delivery of cellular components to the lysosome for degradation. While the UPS has garnered much attention as it relates to neurodegenerative disease, important links between autophagy and neurodegeneration have also become evident. Furthermore, recent studies have revealed interaction between the UPS and autophagy, suggesting a coordinated and complementary relationship between these degradation systems that becomes critical in times of cellular stress. Here we describe autophagy and review evidence implicating this system as an important player in the pathogenesis of neurodegenerative disease. We discuss the role of autophagy in neurodegeneration and review its neuroprotective functions as revealed by experimental manipulation in disease models. Finally, we explore potential parallels and connections between autophagy and the UPS, highlighting their collaborative roles in protecting against neurodegenerative disease.
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Abundant accumulation of autophagic vacuoles in swollen neurons is linked with Aβ/APP-βCTF, suggesting that autophagy clearance is severely disrupted under pathological conditions and is closely linked to amyloid pathology.
“However, the abundant accumulation of autophagic vacuoles in swollen (malnourished) neurons is observed to have a linkage with Aβ/APP-βCTF, suggesting that autophagy clearance is severely disrupted under pathological conditions and is closely linked to amyloid pathology.115,225,230”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [225]
The section on increased autophagic vacuoles describes their massive accumulation in swollen, degenerating neurites in Alzheimer’s disease, but says that this observation alone cannot establish whether autophagic clearance is impaired. The section on animal models reports evidence of impaired autophagosome–lysosome fusion and links APP turnover to toxic amyloid-β; it does not mention APP-βCTF or establish that clearance is severely disrupted. (LLM, conf=0.86)
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References 103 · Cited by 351
- Authors
- Nedelsky, N. B., Todd, P. K., & Taylor, J. P.
- Affiliations
- University of Pennsylvania (US)
- University of Michigan (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Taylor, J. Paul
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 1782
- Issue
- 12
- Pages
- 691-699
- ISSN
- 0925-4439 (ISSN-L)
- PMC
- PMC2621359
- OpenAlex
- W2120180072
- Cited by
- 351
- References
- 103
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 12 · 2023: 21 · 2022: 16 · 2021: 26 · 2020: 21 · 2019: 19 · 2018: 22 · 2017: 21 · 2016: 20 · 2015: 19 · 2014: 31 · 2013: 15 · 2012: 22
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Muscular Dystrophy Association
- National Institutes of Health
- National Institute on Aging (R01AG031587)
- National Institute of Neurological Disorders and Stroke (R01NS053825, NS053825)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- autophagy, ubiquitin-proteasome system, neuroprotection, neurodegenerative diseases, protein degradation, lysosomal degradation, cellular stress, disease models
- MeSH terms
- Animals, Autophagy, Humans, Neuroprotective Agents, Neurodegenerative Diseases, Ubiquitin, Proteasome Endopeptidase Complex
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