Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival

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Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival

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dc.contributor.author Agar, Jeffrey N.
dc.contributor.author Wang, Qi
dc.contributor.author Johnson, Joshua L.
dc.contributor.author Agar, Nathalie Marie Yvonne Rachel
dc.date.accessioned 2011-04-18T04:19:52Z
dc.date.issued 2008
dc.identifier.citation Wang, Qi, Joshua L. Johnson, Nathalie Marie Yvonne Rachel Agar, and Jeffrey N. Agar. 2008. Protein aggregation and protein instability govern familial amyotrophic lateral sclerosis patient survival. PLoS Biology 6(7): e170. en_US
dc.identifier.issn 1544-9173 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4853422
dc.description.abstract The nature of the “toxic gain of function” that results from amyotrophic lateral sclerosis (ALS)-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate) and decreased protein stability (increased likelihood that a protein will unfold), are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pbio.0060170 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2486295/pdf/ en_US
dash.license LAA
dc.subject neurological disorders en_US
dc.title Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Biology en_US
dash.depositing.author Agar, Nathalie Marie Yvonne Rachel
dc.date.available 2011-04-18T04:19:52Z
dash.affiliation.other HMS^Surgery-Brigham and Women's Hospital en_US

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