Restoring functional TDP-43 oligomers in ALS and laminopathic cellular models through baicalein-induced reconfiguration of TDP-43 aggregates.

ABSTRACT: A group of misfolded prone-to-aggregate domains in disease-causing proteins has recently been shown to adopt unique conformations that play a role in fundamental biological processes. These processes include the formation of membrane-less sub-organelles, alternative splicing, and gene activation and silencing. The cellular responses are regulated by the conformational switching of prone-to-aggregate domains, independently of changes in RNA or protein expression levels. Given this, targeting the misfolded states of disease-causing proteins to redirect them towards their physiological conformations is emerging as an effective therapeutic strategy for diseases caused by protein misfolding. In our study, we successfully identified baicalein as a potent structure-correcting agent. Our findings

SUBMITTER: Chang HY 

PROVIDER: S-EPMC10897466 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature