title: Regulation of APP processing. Potential for the therapeutical reduction of brain amyloid burden.
abstract: The role of brain amyloid in the pathogenesis of Alzheimer's disease (AD) is discussed controversially, but combined genetic and biochemical evidence points to a central role of the gene encoding the amyloid precursor APP in at least some forms of AD. This article proposes that preventing brain amyloid formation is a rational concept for drug treatment of AD. We suggest that pharmacologically active ligands for specific cell surface receptor subtypes--normally stimulated by neurotransmitters, growth factors, and cytokines--constitute a class of chemicals that might be useful to accelerate processing of APP into non-amyloidogenic, and biologically active, derivatives. This class of agents includes muscarinic m1 and m3 agonists, serotoninergic 5-HT2a and 5-HT2c agonists, glutamatergic mGluR1 agonists, as well as agonists for bradykinin and vasopressin receptors.
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139, USA. nitsch@zuinh.zuinh.uni-hamburg.de
authors.forename: R M
authors.initials: RM
authors.lastname: Nitsch
authors.forename: R J
authors.initials: RJ
authors.lastname: Wurtman
authors.forename: J H
authors.initials: JH
authors.lastname: Growdon
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D008024:Ligands; D011956:Receptors, Cell Surface