Proliferation of Tau 304-380 Fragment Aggregates through Autocatalytic Secondary Nucleation.

ABSTRACT: The self-assembly of the protein tau into neurofibrillary tangles is one of the hallmarks of Alzheimer's disease and related tauopathies. Still, the molecular mechanism of tau aggregation is largely unknown. This problem may be addressed by systematically obtaining reproducible in vitro kinetics measurements under quiescent conditions in the absence of triggering substances. Here, we implement this strategy by developing protocols for obtaining an ultrapure tau fragment (residues 304-380 of tau441) and for performing spontaneous aggregation assays with reproducible kinetics under quiescent conditions. We are thus able to identify the mechanism of fibril formation of the tau 304-380 fragment at physiological pH using fluorescence spectroscopy and mass spectrometry. We find that primary nucl

SUBMITTER: Rodriguez Camargo DC 

PROVIDER: S-EPMC8640994 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature