Regulation of Amyloid Precursor Protein Processing and Synthesis by Receptor-mediated Signal Transduction
- 作者：Lee ; Robert K. K. ; Araki ; Wataru ; Wurtman ; Richard J.
- 刊名：Neurobiology of Aging
- 出版年：1996
- 期刊代码：202_01974580
- 类别：med
- 出版时间：1996
- 卷：17
- 期：4
- 页码：S201
- 文件大小：101 K
摘要
Aβ peptides which form plaques in Alzheimer's disease (AD) are derived by proteolytic cleavage of a much larger amyloid precursor protein (APP). In cell lines, primary neurons and astrocyte cultures, neurotransmitters that activate cell-surface receptors coupled to phosphotidylinositol (PI) hydrolysis and protein kinase C stimulate secretory cleavage within the Aβ to release the soluble N-terminal ectodomain of APP (APPs) into the extracellular space. We recently showed that trans-(1S,3R)-1-amino-1,3-cyclopentane dicarboxylic acid (ACPD, 100μM), acting on metabotropic glutamate receptor (mGluR) subtypes 1 and 5, which are coupled to PI hydrolysis, approximately doubles the amount of APPs secreted by cultured rat hippocampal neurons or by cortical astrocytes, relative to unstimulated control cells. We now report that cAMP-mediated signal transduction regulates both APP processing and synthesis.