Prion properties of SOD1 in amyotrophic lateral sclerosis and potential therapy

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastatingand rapidly progressive neurodegenerative disease caused by the deterioration of motor neurons. The first symptoms of ALS always begin at a focal but variable site and consistently spread to neighboring regions, suggesting that neurodegeneration in ALS is an orderly and propagating process. Like other neurodegenerative diseases, misfolding of a specific protein is central to ALS. SOD1, the major constituent of the protein deposits in some familial and sporadic forms of ALS, propagates its misfolded conformation like prions, providing a plausible molecular basis for the focalityand spreading of muscle weakness in ALS. Because protein misfolding is a common cause of diverse neurodegenerative diseases, strategies aimed at boosting a cell’ s ability to cope with misfolded proteins could lead to therapeutics to combat these devastating age-related proteinopathies.