Tau aggregation

Class

Tau aggregation inhibitor

Tau is a protein found inside neurons that normally helps hold together microtubules, the internal scaffolding that keeps axons structurally sound and supports transport of materials along nerve fibers. In a group of neurodegenerative diseases called tauopathies—which include Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, and some forms of frontotemporal dementia—tau becomes chemically altered, detaches from microtubules, and misfolds into sticky, beta-sheet-rich clumps. These clumps progress from small soluble aggregates to larger insoluble filaments and eventually to dense deposits called neurofibrillary tangles. The aggregates appear to injure neurons directly and to spread between connected brain cells in a manner reminiscent of infectious prion proteins, and their regional accumulation tracks closely with local nerve cell loss and cognitive symptoms. Tau aggregation inhibitors are small molecules designed to interrupt this misfolding and clumping process, aiming to prevent aggregates from forming, growing, or being passed to neighboring cells. The underlying idea is that stopping aggregation early could slow the spread of damage through brain circuits, offering a disease-modifying effect rather than simply treating symptoms. This approach is under investigation across multiple tauopathies where tau pathology, rather than other disease proteins, is considered the main driver of neurodegeneration.