Targeting oxidative stress to combat neurodegenerative diseases, amyotrophic lateral sclerosis and Huntington’s, for better brain health and recovery

Abstract

Amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD) are among neurodegenerative disorders (NDs) that are progressive, irreversible, debilitating and eventually lethal. Misfolding, aggregation and deposition of proteins such as mutant superoxide dismutase type-1 (SOD1), transactive response DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) in ALS, and mutant huntingtin with polyglutamine expansion in HD, are implicated. Elevated level of reactive oxygen species, causing oxidative stress, is a pathological commonality among several NDs, including ALS and HD, which drives the damage to neuronal cell physiology and homeostasis. In view of its high potential as a therapeutic target, here, we review the role of oxidative stress in the pathogenesis of ALS and HD and the currently pursued therapies targeting oxidative stress, including the FDA-approved drugs and other novel therapeutic strategies presently under investigation.