Tau pathology in neurodegenerative disease: disease mechanisms and therapeutic avenues.

ABSTRACT: Tauopathies are disorders associated with tau protein dysfunction and insoluble tau accumulation in the brain at autopsy. Multiple lines of evidence from human disease, as well as nonclinical translational models, suggest that tau has a central pathologic role in these disorders, historically thought to be primarily related to tau gain of toxic function. However, a number of tau-targeting therapies with various mechanisms of action have shown little promise in clinical trials in different tauopathies. We review what is known about tau biology, genetics, and therapeutic mechanisms that have been tested in clinical trials to date. We discuss possible reasons for failures of these therapies, such as use of imperfect nonclinical models that do not predict human effects for drug development; he

SUBMITTER: Samudra N 

PROVIDER: S-EPMC10266783 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature