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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Title: Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival
Author: Agar, Jeffrey N.; Wang, Qi; Johnson, Joshua L.; Agar, Nathalie Marie Yvonne Rachel

Note: Order does not necessarily reflect citation order of authors.

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.
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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.
Published Version: doi:10.1371/journal.pbio.0060170
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2486295/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4853422

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