Modulation of BACE1 by a Novel Sorting Nexin
Improper trafficking, or sorting, of Alzheimer's disease (AD)-associated proteins, such as beta-amyloid precursor protein (APP) and beta-site APP-cleaving enzyme 1 (BACE1), is associated with the development of AD. BACE1 mediates the first of two cleavage events of APP to yield beta-amyloid peptide. Recent studies suggest that problems with the regulation of the endosome and trans-Golgi network, parts of the cell that are involved in protein sorting, may contribute to the increased beta-amyloid levels associated with AD. Dr. Tae-Wan Kim and colleagues discovered that a member of the phospholipid (fat)-binding sorting nexin family, called Snx6, also binds BACE1 and regulates both its transport within the cell and its ability to complete beta-site cleavage of APP. In addition, these researchers determined that reduction of Snx6 can promote BACE1 generation of beta-amyloid in nerve cells. Dr. Kim's discoveries about these new cell sorting mechanisms may lead to the development of new preventions or treatments for AD.
This paper reports new regulator of BACE1, a key proteolytic enzyme in Alzheimer's disease.
Finan GM, Okada H, Kim T-W. (2011) BACE1 Retrograde Trafficking is Uniquely Regulated by the Cytoplasmic Domain of Sortilin. J. Biol. Chem. 286, 12602-12616.
Di Paolo G, Kim T-W. (2011) Linking lipids to Alzheimer's disease: cholesterol and beyond. Nature Rev. Neurosci. 12, 284-296.
First published on: June 10, 2008
Last modified on: April 7, 2011