Cited by 1,625Autophagy in Disease and TherapyUbiquitin and proteasome pathwaysAlzheimer's disease research and treatments

The roles of intracellular protein-degradation pathways in neurodegeneration

Rubinsztein, David C.·2006·Nature

Abstract

Many late-onset neurodegenerative diseases, including Parkinson's disease and Huntington's disease, are associated with the formation of intracellular aggregates by toxic proteins. It is therefore crucial to understand the factors that regulate the steady-state levels of these 'toxins', at both the synthetic and degradation stages. The degradation pathways acting on such aggregate-prone cytosolic proteins include the ubiquitin-proteasome system and macroautophagy. Dysfunction of the ubiquitin-proteasome or macroautophagy pathways might contribute to the pathology of various neurodegenerative conditions. However, enhancing macroautophagy with drugs such as rapamycin could offer a tractable therapeutic strategy for a number of these diseases.

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Crossref · 10.1038/nature05291

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Authors
Rubinsztein, D. C.
Affiliations
University of Cambridge (GB)
Corresponding author
Rubinsztein, David C.
Venue
Nature
Published
2006-10
Volume
443
Issue
7113
Pages
780-786
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2025714022
Cited by
1,625
References
76
Citations by year
2026: 21 · 2025: 40 · 2024: 35 · 2023: 44 · 2022: 68 · 2021: 66 · 2020: 74 · 2019: 79 · 2018: 64 · 2017: 89 · 2016: 91 · 2015: 114 · 2014: 106 · 2013: 116 · 2012: 119
FWCI
12.03
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
Wellcome Trust
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
neurodegeneration, protein degradation, ubiquitin-proteasome system, macroautophagy, protein aggregates, Parkinson's disease, Huntington's disease, rapamycin, treatment options
MeSH terms
Huntingtin Protein, Animals, Autophagy, Humans, Lysosomes, Nerve Tissue Proteins, Nuclear Proteins, Neurodegenerative Diseases, Ubiquitin, Proteasome Endopeptidase Complex

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