Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease.

ABSTRACT: Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification of a class of compounds called ReS19-T, which are able to restore calcium homeostasis in cell-based models of tau pathology. Aberrant tau accumulation leads to uncontrolled activation of store-operated calcium channels (SOCCs) by remodeling septin filaments at the cell cortex. Binding of ReS19-T to septins restores filament assembly in the disease state and restrains calcium entry through SOCCs. In amyloid-β and tau-driven mouse models of disease, ReS19-T agents restored synaptic plasticity, normalized brain network activity, and attenuated the development of both amyloid-β and tau pathology. Our findings identify the septin cytoskeleton as a potential therapeuti

SUBMITTER: Princen K 

PROVIDER: S-EPMC11827694 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature