Abstract
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 Aβ generation by specifically targeting the substrate (APP) instead of the enzyme (β- or γ-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 Aβ.
Original language | English (US) |
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Pages (from-to) | 208-219 |
Number of pages | 12 |
Journal | Experimental Neurology |
Volume | 185 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2004 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Neurology
- Developmental Neuroscience