Initiation of transthyretin aggregation at neutral pH by fluid agitation.

ABSTRACT: The transthyretin (TTR) tetramer, assembled as a dimer of dimers, transports thyroxine and retinol binding protein in blood plasma and cerebrospinal fluid. Aggregation of wild type (WT) or pathogenic variant TTR leads to transthyretin amyloidosis, which is associated with neurodegenerative and cardiac disease. The trigger for TTR aggregation under physiological conditions is unknown. The tetramer is extremely stable at neutral pH, but aggregation via tetramer dissociation and monomer misfolding can be induced in vitro by lowering the pH. To elucidate factors that may cause TTR aggregation at neutral pH, we examined the effect of shear forces such as those that arise from fluid flow in the vascular system. Fluid shear forces were generated by rapidly stirring TTR solutions in conical microc

SUBMITTER: Ritsch I 

PROVIDER: S-EPMC11929447 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature