GPX4 deficiency-dependent phospholipid peroxidation drives motor deficits of ALS.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by oxidative stress that triggers motor neurons loss in the brain and spinal cord. However, the mechanisms underlying the exact role of oxidative stress in ALS-associated neural degeneration are not definitively established. Oxidative stress-generated phospholipid peroxides are known to have extensive physiological and pathological consequences to tissues. Here, we discovered that the deficiency of glutathione peroxidase 4 (GPX4), an essential antioxidant peroxidase, led to the accumulation of phospholipid peroxides and resulted in a loss of motor neurons in spinal cords of ALS mice. Mutant human SOD1^G93A transgenic mice were intrathecally injected with neuron-targeted adeno-associated v

SUBMITTER: Tu LF 

PROVIDER: S-EPMC9811330 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature