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 (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.
Stephenson
Vanessa C
VC
Department of Chemistry, Dalhousie University, Halifax, NS, Canada B3H 4J3.
Heyding
R Andrew
RA
Weaver
Donald F
DF
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015195:Drug Design; D006493:Heparin / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism
D004364:Pharmaceutical Preparations; D011956:Receptors, Cell Surface; D006493:Heparin