ALDH3A1-mediated detoxification of reactive aldehydes contributes to distinct muscle responses to denervation and Amyotrophic Lateral Sclerosis progression.

ABSTRACT: Different muscles exhibit varied susceptibility to degeneration in Amyotrophic Lateral Sclerosis (ALS), a fatal neuromuscular disorder. Extraocular muscles (EOMs) are particularly resistant to ALS progression and exploring the underlying molecular nature may deliver great therapeutic value. Reactive aldehyde 4-hydroxynonenal (HNE) is implicated in ALS pathogenesis and ALDH3A1 is an inactivation-resistant intracellular detoxifier of 4-HNE protecting eyes against UV-induced oxidative stress. Here we detected prominently higher levels of ALDH3A1 in mouse EOMs than other muscles under normal physiological conditions. In an ALS mouse model (hSOD1^G93A) reaching end-stage, ALDH3A1 expression was sustained at high level in EOMs, whereas substantial upregulation of ALDH3

SUBMITTER: Li A 

PROVIDER: S-EPMC11642873 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature