The "promiscuous drug concept" with applications to Alzheimer's disease

Arguably, Alzheimer's disease (AD) is a multifactorial syndrome, rather than single disease, arising from a complex array of neurochemical factors. Numerous studies on the molecular pathogenesis of AD implicate a diversity of factors ranging from neurotoxic peptides (P-amyloid) to inflammatory processes (interleukins), but all culminating in a common neuropathology. This diversity of molecular causation is an impediment to the design of effective therapies for AD. To address this design problem, we sought to identify a single, common motif (a "common receptor") shared by multiple structurally and functionally diverse proteins implicated in AD. This search revealed the presence of a common BBXB peptide motif and upon refinement, an AXBBXB motif;, these regions can be exploited for the design of a "promiscuous drug" that exploits a "one-drug-multiplereceptors" therapeutic strategy for AD. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.