M1 muscarinic acetylcholine receptor interacts with BACE1 and regulates its proteosomal degradation
- 生物医学－已发表论文 
A prime culprit in the pathogenesis of Alzheimer's disease (AD) is overproduction/aggregation of beta-amyloid (A beta), which is derived from beta-Amyloid Precursor Protein through sequential cleavages by beta-site APP cleaving protein 1 (BACE1) and gamma-secretase. The level/activity of BACE1 is elevated in sporadic AD and identification of proteins that affect BACE1 is important in AD research. Here we found that M1 Muscarinic acetylcholine receptor (M1 mAChR), an important G protein-coupled receptor involved in cholinergic neuronal activity, can interact with BACE1 and mediate its proteosomal degradation. Moreover, overexpression and downregulation of M1 mAChR can decrease and increase the levels of BACE1, as well as the generation of A beta, respectively. These findings point to a novel coupling of BACE1 and M1 mAChR in AD and possibly schizophrenia. (C) 2012 Elsevier Ireland Ltd. All rights reserved.