title: A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease.
abstract: Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model.
authors.affiliation: Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Marguerite
authors.initials: M
authors.lastname: Prior
authors.forename: Richard
authors.initials: R
authors.lastname: Dargusch
authors.forename: Amanda
authors.initials: A
authors.lastname: Roberts
authors.forename: Roland
authors.initials: R
authors.lastname: Riek
authors.forename: Cédric
authors.initials: C
authors.lastname: Eichmann
authors.forename: Chandramouli
authors.initials: C
authors.lastname: Chiruta
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Akaishi
authors.forename: Kazuho
authors.initials: K
authors.lastname: Abe
authors.forename: Pamela
authors.initials: P
authors.lastname: Maher
authors.forename: David
authors.initials: D
authors.lastname: Schubert
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D017774:Long-Term Potentiation / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012995:Solubility / Q000187:drug effects; D013329:Structure-Activity Relationship; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; C529348:CNB 001; D006360:Heat-Shock Proteins; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D016877:Oxidants; D011720:Pyrazoles; D003474:Curcumin