Molecular mechanisms underlying the impact of mutations in SOD1 on its conformational properties associated with amyotrophic lateral sclerosis as revealed with molecular modelling

摘要

BackgroundSo far, little is known about the molecular mechanisms of amyotrophic lateral sclerosis onset and progression caused by SOD1 mutations. One of the hypotheses is based on SOD1 misfolding resulting from mutations and subsequent deposition of its cytotoxic aggregates. This hypothesis is complicated by the fact that known SOD1 mutations of similar clinical effect could be distributed over the whole protein structure.