Cilostazol, a phosphodiesterase 3 inhibitor, activates proteasome-mediated proteolysis and attenuates tauopathy and cognitive decline.

ABSTRACT: Alzheimer's disease and several variants of frontotemporal degeneration including progressive supranuclear palsy and corticobasal degeneration are characterized by the accumulation of abnormal tau protein into aggregates. Most proteins, including tau, are degraded via the ubiquitin proteasome system, but when abnormal tau accumulates, the function of 26S proteasomes is downregulated. The negative effect of tau aggregates on the function of the proteasome can have deleterious consequences on protein homeostasis and disease progression. Developing therapies aimed at clearing abnormal tau are thus of considerable interest. In the present study, we investigated the effect of cilostazol, an FDA-approved selective phosphodiesterase 3 inhibitor, on a mouse model of tauopathy (line rTg4510). Admin

SUBMITTER: Schaler AW 

PROVIDER: S-EPMC10075247 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature