Cited by 270Heat shock proteins researchProtein purification and stabilityPrion Diseases and Protein Misfolding

Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins

Open access
Ciryam, Prajwal, Tartaglia, Gian Gaetano, Morimoto, Richard I., Dobson, Christopher M., Vendruscolo, Michele·2013·Cell Reports

Abstract

The maintenance of protein solubility is a fundamental aspect of cellular homeostasis because protein aggregation is associated with a wide variety of human diseases. Numerous proteins unrelated in sequence and structure, however, can misfold and aggregate, and widespread aggregation can occur in living systems under stress or aging. A crucial question in this context is why only certain proteins appear to aggregate readily in vivo, whereas others do not. We identify here the proteins most vulnerable to aggregation as those whose cellular concentrations are high relative to their solubilities. We find that these supersaturated proteins represent a metastable subproteome involved in pathological aggregation during stress and aging and are overrepresented in biochemical processes associated with neurodegenerative disorders. Consequently, such cellular processes become dysfunctional when the ability to keep intrinsically supersaturated proteins soluble is compromised. Thus, the simultaneous analysis of abundance and solubility can rationalize the diverse cellular pathologies linked to neurodegenerative diseases and aging.

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 · 10.1016/j.celrep.2013.09.043

Cites

66 of 66 references verified0 citation errors · 0 not checkable

Statistics

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?

  • The high solubility of abundant proteins is insufficient to protect them from age-dependent aggregation, as they eventually exceed critical concentrations (supersaturation).

    “Apparently, the high solubility of abundant proteins is insufficient to protect them from age-dependent aggregation, as eventually these proteins exceed their critical concentrations, a phenomenon referred to as ‘supersaturation’ (Ciryam et al., 2013).”

    From Widespread Proteome Remodeling and Aggregation in Aging C. elegans (2015) · cites this paper as Ciryam et al., 2013

  • Proteome remodeling promotes aggregation by pushing some proteins above a solubility threshold, i.e., supersaturation.

    “Importantly, proteome remodeling acts as a driver of aggregation by raising the level of a subset of proteins beyond a critical solubility limit (‘supersaturation’) (Ciryam et al., 2013) (Figure 7D).”

    From Widespread Proteome Remodeling and Aggregation in Aging C. elegans (2015) · cites this paper as Ciryam et al., 2013

Self-check

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

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

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Ciryam, P., Tartaglia, G. G., Morimoto, R. I., Dobson, C. M., & Vendruscolo, M.
Affiliations
  • Northwestern University (US)
  • Universitat Pompeu Fabra (ES)
  • University of Cambridge (GB)
Corresponding author
  • Morimoto, Richard I.
  • Dobson, Christopher M.
  • Vendruscolo, Michele
Venue
Cell Reports
Publisher
Elsevier BV
Published
2013-11
Volume
5
Issue
3
Pages
781-790
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2146554687
Cited by
270
References
66
Citations by year
2026: 10 · 2025: 12 · 2024: 14 · 2023: 29 · 2022: 29 · 2021: 29 · 2020: 16 · 2019: 28 · 2018: 22 · 2017: 20 · 2016: 18 · 2015: 25 · 2014: 18
FWCI
9.10
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, cc-by)
Funders
  • Ellison Medical Foundation
  • Wellcome Trust (089703)
  • US-UK Fulbright Commission
  • National Institutes of Health
  • Directorate for Biological Sciences
  • Biotechnology and Biological Sciences Research Council (BB/H003843/1)
  • National Institute on Aging (R37AG026647, R01AG026647)
  • National Institute of General Medical Sciences (R01GM038109, R37GM038109)
  • National Institute of Neurological Disorders and Stroke
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
Keywords
protein aggregation, protein solubility, neurodegenerative diseases, aging, protein misfolding, protein abundance, cellular stress, proteostasis
MeSH terms
Humans, Proteins, Protein Folding, Neurodegenerative Diseases

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