Gasdermin D is activated but does not drive neurodegeneration in SOD1^G93A model of ALS: Implications for targeting pyroptosis.

ABSTRACT: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, microgliosis, and neuroinflammation. While pyroptosis, an inflammatory form of programmed cell death, has been implicated in ALS, the specific role of Gasdermin D (GSDMD) - the primary executioner of pyroptosis - remains unexplored. In this study, we examined the function of GSDMD in the well-established SOD1^G93A mouse model of ALS. Our results showed robust GSDMD activation in the spinal cords of SOD1^G93A animals with elevated expression in Iba1+ microglia. To explore its role in disease progression, we bred C57Bl/6 J.SOD1^G93A mice onto a C57Bl/6NJ.GSDMD-deficient background. In comparing SOD1^G93A; Gsdmd+/+ and SOD1^G93A</

SUBMITTER: Gunner G 

PROVIDER: S-EPMC12412056 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature