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

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The roles of intracellular protein-degradation pathways in neurodegeneration

Rubinsztein, David C.·2006·Nature

DOI 10.1038/nature05291

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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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Authors: Rubinsztein, D. C.
Affiliations: University of Cambridge (GB)
Corresponding author: Rubinsztein, David C.
ORCID: Rubinsztein, David C.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2006-10
Volume: 443
Issue: 7113
Pages: 780-786
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature05291
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
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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The roles of intracellular protein-degradation pathways in neurodegeneration

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