title: Small molecule neurotrophin receptor ligands: novel strategies for targeting Alzheimer's disease mechanisms.
abstract: A number of factors limit the therapeutic application of neurotrophin proteins, such as nerve growth factor (NGF) and brain-derived growth factor (BDNF), for Alzheimer's and other neurodegenerative diseases. These factors include unfavorable pharmacological properties typical of proteins and the pleiotropic effects mediated by protein-ligand interactions with p75(NTR), Trk, and sortilin neurotrophin receptors. Targeted modulation of p75(NTR) provides a strategy for preventing degeneration without promoting TrkA-mediated deleterious effects, and targeted activation of TrkB might achieve more favorable neurotrophic effects than those achieved by concomitant activation of p75(NTR) and TrkB. The discovery of small molecules functioning as ligands at specific neurotrophin receptors has made possible for the first time approaches for modulating selected components of neurotrophin signaling processes for the purpose of modulating underlying Alzheimer's disease mechanisms.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA. longo@stanford.edu
authors.forename: Frank M
authors.initials: FM
authors.lastname: Longo
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Juliet K
authors.initials: JK
authors.lastname: Knowles
authors.forename: Youmei
authors.initials: Y
authors.lastname: Xie
authors.forename: Laura A
authors.initials: LA
authors.lastname: Moore
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Massa
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D006801:Humans; D008024:Ligands; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects* / Q000627:therapeutic use*
chemical_list: D008024:Ligands; D018696:Neuroprotective Agents; D017475:Receptors, Nerve Growth Factor