Clinical spectrum of individuals with pathogenic
N
F1
missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype–phenotype study in neurofibromatosis type 1
Human Mutation | October 9, 2019 | Volume: 41 | Issue: 1 | Pages: 299-315
High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype–Phenotype Correlation
Human Mutation | July 14, 2015 | Volume: 36 | Issue: 11 | Pages: 1052-1063
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.