Upregulating ANKHD1 in PS19 mice reduces Tau phosphorylation and mitigates Tau-toxicity-induced cognitive deficits.

ABSTRACT: Abnormal accumulation of Tau protein in the brain disrupts normal cellular function and leads to neuronal death linked with many neurodegenerative disorders such as Alzheimer's disease. An attractive approach to mitigate Tau-induced neurodegeneration is to enhance the clearance of toxic Tau aggregates. We previously showed that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration in fly disease models. Here we have generated a transgenic mouse line carrying Cre-inducible ANKHD1, the mouse homolog of mask, to determine whether the protective role of mask is conserved from flies to mammals. Utilizing the TauP301S-PS19 mouse model for Tau-related dementia, we observed that ANKHD1 significantly reduced hyperphosphorylated human

SUBMITTER: Tian X 

PROVIDER: S-EPMC11601383 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature