A prion-like mechanism for the propagated misfolding of SOD1 from in silico modeling of solvated near-native conformers.

ABSTRACT: A prion-like mechanism has been developed to explain the observed promotion of amyloid aggregation caused by conversion of structurally intact SOD1 to a misfolded form. Superoxide dismutase [Cu-Zn], or SOD1, is a homo-dimeric protein that functions as an antioxidant by scavenging for superoxide. The misfolding and aggregation of SOD1 is linked to inherited, or familial, amyotrophic lateral sclerosis (FALS), a progressive and fatal neurodegenerative disease. Aberrant SOD1 folding has also been strongly implicated in disease causation for sporadic ALS, or SALS, which accounts for ~90% of ALS cases. Studies have found that mutant, misfolded SOD1 can convert wtSOD1 in a prion-like fashion, and that misfolded wtSOD1 can be propagated by release and uptake of protein aggregates. Here it is demon

SUBMITTER: Healy EF 

PROVIDER: S-EPMC5417709 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature