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The Endocytic Protein Numb Regulates App Metabolism And Notch Signaling: Implications For Alzheimer's Disease, George Kyriazis
The Endocytic Protein Numb Regulates App Metabolism And Notch Signaling: Implications For Alzheimer's Disease, George Kyriazis
Electronic Theses and Dissertations
Increased production of amyloid beta (A-beta) peptide, via altered proteolytic cleavage of amyloid protein precursor (APP), and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch1, a membrane receptor that controls cell fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase protein complex in which mutations cause early-onset inherited AD. Numb is an evolutionarily conserved endocytic adapter involved in the internalization of transmembrane receptors. Mammals produce four Numb isoforms that differ in two functional domains, a phosphotyrosine-binding domain (PTB) and a …