The X11 proteins, A[beta] production and Alzheimer's disease

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tins.2006.03.001 Byline: Christopher C.J. Miller, Declan M. McLoughlin, Kwok-Fai Lau, Maria E. Tennant, Boris Rogelj Abstract: Cerebral deposition of amyloid-[beta] peptide (A[beta]) within neuritic plaques is a hallmark pathology of Alzheimer's disease. It is now generally believed that the development of this pathology is central to the pathogenesis of Alzheimer's disease. As such, inhibiting A[beta] deposition or removing A[beta] deposits once they are formed represent therapeutic targets for Alzheimer's disease. A[beta] is derived from a precursor, the amyloid precursor protein (APP), and APP binds to the X11 family of adaptor proteins. Studies from several laboratories have now shown that X11[alpha] and X11[beta] (the two neuronal X11s) inhibit APP processing and A[beta] production. Exactly how this is achieved is not yet known but recent studies in which other X11 binding partners have been identified are beginning to reveal potential mechanisms. Author Affiliation: MRC Centre for Neurodegeneration Research, Departments of Neuroscience and Section of Old Age Psychiatry PO37, Institute of Psychiatry, King's College, De Crespigny Park, Denmark Hill, London SE5 8AF, UK