期刊
BRAIN RESEARCH REVIEWS
卷 48, 期 2, 页码 257-264出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainresrev.2004.12.016
关键词
Alzheimer's disease; signal transduction; ShcA; neurodegeneration
资金
- Telethon [E.1144] Funding Source: Medline
The amyloid precursor protein (APP) is an ubiquitous receptor-like molecule involved in the pathogenesis of Alzheimer's disease that generates beta-amyloid peptides and causes plaque formation. APP and some of its C-terminal proteolytic fragments (CTFs) have also been shown to be in the center of a complex protein-protein network, where selective phosphorylation of APP C-terminus may regulate the interaction with cytosolic phosphotyrosine binding (PTB) domain or Sre homology 2 (SH2) domain containing proteins involved in cell signaling. We have recently described an interaction between tyrosine-phosphorylated CTFs and ShcA adaptor protein which is highly enhanced in AD brain, and a new interaction between APP and the adaptor protein Grb2 both in human brain and in neuroblastoma cultured cells. These data suggest a possible role in cell signaling for APP and its CTFs, in a manner similar to that previously reported for other receptors, through a tightly regulated coupling with intracellular adaptors to control the signaling of the cell. In this review, we discuss the significance of these novel findings for AD development. (c) 2004 Published by Elsevier B.V.
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