Adaptor protein interactions: modulators of amyloid precursor protein metabolism and Alzheimer's disease risk?
The cytoplasmic C-terminus of APP plays critical roles in its cellular trafficking and delivery to proteases. Adaptor proteins with phosphotyrosine-binding (PTB) domains, including those in the X11, Fe65, and c-Jun N-terminal kinase (JNK)-interacting protein (JIP) families, bind specifically to the absolutely conserved -YENPTY- motif in the APP C-terminus to regulate its trafficking and processing. Compounds that modulate APP-adaptor protein interactions may inhibit Abeta generation by specifically targeting the substrate (APP) instead of the enzyme (beta- or gamma-secretase). Genetic polymorphisms in (or near) adaptor proteins may influence risk of sporadic AD by interacting with APP in vivo to modulate its trafficking and processing to Abeta.
King
Gwendalyn D
GD
Neuroscience Program, University of Michigan, Ann Arbor, MI 48105, USA.
Scott Turner
R
R
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D012307:Risk Factors
D033942:Adaptor Proteins, Vesicular Transport; D016564:Amyloid beta-Protein Precursor