Title: Dysfunction of G Protein-Coupled Receptor Kinases in Alzheimer?s Disease Tags:accumulation & beta amyloid & brain inflammation & cognitive decline & cognitive impairment & correlates & desensitization & g protein coupled receptor & interface & mitochondria & neurofibrillary tangles & pathogenesis & protein coupled receptor & signal transduction Go to article The signal transduction deficits in Alzheimer?s disease (AD) converge to the receptor-G protein interface, where G protein-coupled receptor kinases (GRKs) act. Beta-Amyloid can decrease membrane and increase cytosolic GRK2/5. GRK2 accumulates near damaged mitochondria and neurofibrillary tangles, and correlates with cognitive decline. The GRK5 deficiency impairs presynaptic M2 desensitization, reduces acetylcholine release, and leads to cholinergic degeneration and cognitive impairment. It also promotes Beta-amyloid accumulation and exaggerates brain inflammation; therefore, it appears to be closely involved in the AD pathogenesis.