Pathologic tau conformer ensembles induce dynamic, liquid-liquid phase separation events at the nuclear envelope.

ABSTRACT:

Background

The microtubule-associated protein tau forms aggregates in different neurodegenerative diseases called tauopathies. Prior work has shown that a single P301L mutation in tau gene, MAPT, can promote alternative tau folding pathways that correlate with divergent clinical diagnoses. Using progressive chemical denaturation, some tau preparations from the brain featured complex transitions starting at low concentrations of guanidine hydrochloride (GdnHCl) denaturant, indicating an ensemble of differently folded tau species called conformers. On the other hand, brain samples with abundant, tangle-like pathology had simple GdnHCl unfolding profile resembling the profile of fibrillized recombinant tau and suggesting a unitary conformer composition. In studies here we sought to un

SUBMITTER: Kang SG 

PROVIDER: S-EPMC8428099 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature