The "promiscuous drug concept" with applications to Alzheimer's disease |
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Authors: | Stephenson Vanessa C Heyding R Andrew Weaver Donald F |
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Institution: | Department of Chemistry, Dalhousie University, Halifax, NS, Canada B3H 4J3. |
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Abstract: | 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 (beta-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-multiple-receptors" therapeutic strategy for AD. |
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Keywords: | Alzheimer’s disease Drug design Pathogenesis BBXB motif AXBBXB motif Common receptor |
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