A Longitudinal Study of Sex Differences in a TDP-43 Mouse Model Reveals STI1 Regulation of TDP-43 Proteinopathy and Motor Deficits.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a disease influenced by a complex interplay of age, genetics, and sex. Most ALS cases are sporadic, and individuals with this disease show elevated levels of TDP-43 in their central nervous system and aggregated cytoplasmic inclusions containing TDP-43 in neurons. Misfolded and aggregated proteins like TDP-43 can be refolded or marked for degradation by molecular chaperones and their co-chaperone partners. In this study, we use a mouse model of ALS that mildly overexpresses human wild-type TDP-43 in neurons to explore how aging affects the onset of motor abnormalities and proteinopathy in male and female mice. We found that the age-dependent onset of motor symptoms is more pronounced in male mice, despite both sexes sharing similar TDP-43 pathology. F

SUBMITTER: Novikov V 

PROVIDER: S-EPMC12374248 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature