Scientists pinpoint key hotspot driving tau propagation in dementia - News-Medical
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Diseases such as Alzheimer's and frontotemporal dementia are considered neurodegenerative tauopathies, in which tau proteins in the brain misfold and lead to cognitive decline. Until now, it has been unclear how misfolded tau recruits other seemingly healthy tau and causes it to misfold and clump.
A new study led by Northwestern University researchers, in collaboration with researchers with the University of California, Santa Barbara, found that tau vulnerable to misfolding carries a single dominant hotspot. That site binds the matching site on a neighboring tau, or on a tau at the end of an existing fibril, and the incoming tau then misfolds to match. The hotspot is hydrated by water that is wrapping over and protecting a hydrophobic site, and releasing that water is what pulls the two together. This finding could help scientists diagnose tauopathies, block misfolded tau from converting other normal tau to misfolded shapes, and design therapeutic solutions in the future.
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