Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS Biol. 2008 Jul 29;6(7):e170. doi: 10.1371/journal.pbio.0060170.

Protein aggregation and protein instability govern familial amyotrophic lateral sclerosis patient survival.

Author information

  • 1Department of Chemistry, Brandeis University, Waltham, Massachusetts, USA.

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.

Comment in

PMID:
18666828
[PubMed - indexed for MEDLINE]
PMCID:
PMC2486295
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk