Levosimendan inhibits disulfide tau oligomerization and ameliorates tau pathology in Tau^P301L-BiFC mice.

ABSTRACT: Tau oligomers play critical roles in tau pathology and are responsible for neuronal cell death and transmitting the disease in the brain. Accordingly, preventing tau oligomerization has become an important therapeutic strategy to treat tauopathies, including Alzheimer's disease. However, progress has been slow because detecting tau oligomers in the cellular context is difficult. Working toward tau-targeted drug discovery, our group has developed a tau-BiFC platform to monitor and quantify tau oligomerization. By using the tau-BiFC platform, we screened libraries with FDA-approved and passed phase I drugs and identified levosimendan as a potent anti-tau agent that inhibits tau oligomerization. ¹⁴C-isotope labeling of levosimendan revealed that levosimendan covalently bound to tau

SUBMITTER: Lim S 

PROVIDER: S-EPMC10073126 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature