Mechanism of GRK2 aggregation in Alzheimer disease
It is not clear on the role of G-protein-coupled receptor kinase 2 (GRK2) in cell growth and survival.
The researchers find increased dysfunctional protein aggregates of GRK2 in Alzheimer brains and in AD mice and is induced by two hallmark proteins of AD: beta-amyloid and the neurofibrillary-tangle-inducing, TAU-P301L.
Aggregated phospho-S670-GRK2 triggers aggregation of TOMM6 (translocase of outer mitochondrial membrane 6) that promotes causing mitochondrial dysfunction and enhanced beta-amyloid accumulation.
Prevention of dysfunctional GRK2 aggregation by transgenic techniques and small molecules retards neurodegeneration, reduces neuronal loss, and prolongs survival.
https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00124-2
