Polyserine domains are toxic and exacerbate tau pathology in mice.

ABSTRACT: Polyserine domains mediate the association of some nuclear RNA-binding proteins with cytoplasmic tau aggregates occurring in tauopathy models and patient samples. In cell lines, polyserine domains mediate colocalization with tau aggregates and promote formation, suggesting that the cytoplasmic mislocalization of polyserine-containing proteins could contribute to human disease. Moreover, polyserine can be produced by repeat-associated non-AUG translation in CAG repeat expansion diseases. However, whether polyserine expressed in a mammalian brain is toxic and/or can exacerbate tau pathology is unknown. We used AAV9-mediated delivery to express a 42-repeat polyserine protein in wild-type and tau transgenic mouse models. We observe that polyserine expression has toxic effects in wild-type anim

SUBMITTER: Van Alstyne M 

PROVIDER: S-EPMC12773705 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature