Chaperoning of specific tau structure by immunophilin FKBP12 regulates the neuronal resilience to extracellular stress.

ABSTRACT: Alzheimer's disease and related tauopathies are characterized by the pathogenic misfolding and aggregation of the microtubule-associated protein tau. Understanding how endogenous chaperones modulate tau misfolding could guide future therapies. Here, we show that the immunophilin FKBP12, the 12-kDa FK506-binding protein (also known as FKBP prolyl isomerase 1A), regulates the neuronal resilience by chaperoning a specific structure in monomeric tau. Using a combination of mouse and cell experiments, in vitro aggregation experiments, nuclear magnetic resonance-based structural analysis of monomeric tau, site-specific phosphorylation and mutation, as well as structure-based analysis using the neural network-based structure prediction program AlphaFold, we define the molecular factors that gover

SUBMITTER: Jiang L 

PROVIDER: S-EPMC9891691 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature