Mutant TDP-43 drives impairments in axonal transport and glycolysis in a mouse stem-cell-derived motor neuron model of amyotrophic lateral sclerosis (ALS).

ABSTRACT: TDP-43 dysfunction is thought to be central to ALS pathogenesis. Studying mutations in the gene which encodes TDP-43, TARDBP, provides a valuable opportunity to gain insight into how TDP-43 dysfunction alters cellular homoeostasis. Our group has previously developed a TDP-43^M337V mouse embryonic stem cell-derived motor neuron (mESC-MN) model, which expresses a single copy of the human TARDBP gene expressing the pathogenic M337V mutation at low levels. Here, we perform extensive phenotypic characterisation of this model, and show that TDP-43^M337V leads to reduced MN viability, impaired axonal transport and reduced basal glycolysis compared to TDP-43^WT controls. Altered neuronal viability and function occurs in the absence of TDP-43 mislocalisation or aggrega

SUBMITTER: Carroll E 

PROVIDER: S-EPMC12877184 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature