Citations 1
α 2A adrenergic receptor promotes amyloidogenesis through disrupting APP-SorLA interaction
Peng, Yin, Che, Pulin , Gannon, Mary , Liu, Yin , Li, Ling , Bu, Guojun , Groen, Thomas van , Jiao, Kai , Wang, Qin , Chen, Yunjia , Peng, Yin, Bu, Guojun
Proceedings of the National Academy of Sciences | November 20, 2014 | Volume: 111 | Issue: 48 | Pages: 17296-17301
Significance Endocytic sorting of amyloid precursor protein (APP) governed by the vacuolar protein sorting (Vps10) family of receptors plays a decisive role in controlling the outcome of APP proteolytic processing and the generation of amyloid β (Aβ) peptides, the key pathogenic factor of Alzheimer's disease (AD). This study provides the first evidence to our knowledge that a G protein-coupled receptor, namely, the α 2A adrenergic receptor, modulates APP endocytic sorting and promotes Aβ generation through disrupting APP interaction with a Vps10 family protein, sorting-related receptor with A repeat. Significantly, blockade of α 2A AR by a clinical antagonist reduces AD-related pathology and ameliorates cognitive deficits in an AD transgenic model, suggesting repurposing clinical α 2 AR antagonists as a new direction for AD treatment.