Cited by 215Autophagy in Disease and TherapyGenetics, Aging, and Longevity in Model OrganismsUbiquitin and proteasome pathways

The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.

p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects

Open access

Abstract

Suppression of macroautophagy, due to mutations or through processes linked to aging, results in the accumulation of cytoplasmic substrates that are normally eliminated by the pathway. This is a significant problem in long-lived cells like neurons, where pathway defects can result in the accumulation of aggregates containing ubiquitinated proteins. The p62/Ref(2)P family of proteins is involved in the autophagic clearance of cytoplasmic protein bodies or sequestosomes. These unique structures are closely associated with protein inclusions containing ubiquitin as well as key components of the autophagy pathway. In this study we show that detergent fractionation followed by western blot analysis of insoluble ubiquitinated proteins (IUP), mammalian p62 and its Drosophila homologue, Ref(2)P can be used to quantitatively assess the activity level of aggregate clearance (aggrephagy) in complex tissues. Using this technique we show that genetic or age-dependent changes that modify the long-term enhancement or suppression of aggrephagy can be identified. Moreover, using the Drosophila model system this method can be used to establish autophagy-dependent protein clearance profiles that are occurring under a wide range of physiological conditions including developmental, fasting and altered metabolic pathways. This technique can also be used to examine proteopathies that are associated with human disorders such as frontotemporal dementia, Huntington and Alzheimer disease. Our findings indicate that measuring IUP profiles together with an assessment of p62/Ref(2)P proteins can be used as a screening or diagnostic tool to characterize genetic and age-dependent factors that alter the long-term function of autophagy and the clearance of protein aggregates occurring within complex tissues and cells.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.4161/auto.7.6.14943

Cites

74 of 74 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 74 references

Research works printed but not linked: 4

  1. Zerovnik E, 2009, Curr Alzheimer Res
  2. Clausen TH, 2010, Autophagy, 6
  3. Seelaar H, 2009, J Neurol
  4. Rusten TE, 2007, Autophagy, 4

Cited by

Sorted by citations

Items 101–200 of 215

Metadata

Authors
Bartlett, B. J., Isakson, P., Lewerenz, J., Sanchez, H., Kotzebue, R. W., Cumming, R. C., Harris, G. L., Nezis, I. P., Schubert, D. R., Simonsen, A., & Finley, K. D.
Affiliations
  • San Diego State University (US)
  • University of Oslo (NO)
  • Salk Institute for Biological Studies (US)
Venue
Autophagy
Published
2011-06
Volume
7
Issue
6
Pages
572-583
ISSN
  • 1554-8627 (ISSN-L)
  • 1554-8635
OpenAlex
W2014829450
Cited by
215
References
74
Citations by year
2026: 8 · 2025: 14 · 2024: 13 · 2023: 15 · 2022: 15 · 2021: 17 · 2020: 13 · 2019: 13 · 2018: 15 · 2017: 12 · 2016: 22 · 2015: 17 · 2014: 18 · 2013: 11 · 2012: 12
FWCI
9.84
Type
journal article
Language
en
Open access
Locations
  • Autophagy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Scholarship@Western (Western University) (submittedVersion)
Funders
National Institute on Aging (R21AG030187, R01AG033283, R44AG033427, R43AG033427, R01AG039628)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
p62, neuronal aging, aggrephagy, protein aggregate clearance, ubiquitinated proteins, autophagy defects, Drosophila, frontotemporal dementia, Huntington's disease, Alzheimer's disease, proteinopathies
MeSH terms
Sequestosome-1 Protein, Alzheimer Disease, Animals, Autophagy, Cytoplasm, Detergents, DNA-Binding Proteins, Drosophila melanogaster, Humans, Models, Biological, Models, Genetic, Mutation, Neurons, Nuclear Proteins, Time Factors, Gene Expression Regulation, Developmental, Drosophila Proteins, Animals, Genetically Modified, Microscopy, Electron, Transmission, Adaptor Proteins, Signal Transducing

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review