Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins

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• dc.contributor.author Ciryam, Prajwalca
• dc.contributor.author Tartaglia, Gian Gaetanoca
• dc.contributor.author Morimoto, Richard I.ca
• dc.contributor.author Dobson, Christopher M.ca
• dc.contributor.author Vendruscolo, Micheleca
• dc.date.accessioned 2014-06-03T07:24:02Z
• dc.date.available 2014-06-03T07:24:02Z
• dc.date.issued 2013ca
• dc.description.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.
• dc.description.sponsorship P.C. was supported by grants from the US-UK Fulbright Commission and St. John’s College, University of Cambridge. R.I.M. was supported by grants from the National Institutes of Health (NIGMS, NIA, and NINDS), the Ellison Medical Foundation, and the Daniel F. and Ada L. Rice Foundation. C.M.D. and M.V. were supported by grants from the Wellcome Trust and the UK Biotechnology and Biological Sciences Research Council.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Ciryam P, Tartaglia GG, Morimoto RI, Dobson CM, Vendruscolo M. Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins. Cell Rep. 2013; 5(3):781-790. DOI: 10.1016/j.celrep.2013.09.043ca
• dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2013.09.043
• dc.identifier.issn 2211-1247ca
• dc.identifier.uri http://hdl.handle.net/10230/22556
• dc.language.iso engca
• dc.publisher Elsevierca
• dc.relation.ispartof Cell Reports. 2013;5(3):781-790
• dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/3.0/
• dc.subject.other Sistema nerviós -- Degeneració
• dc.subject.other Proteïnes
• dc.title Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteinsca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca