Neuropsychology Abstract of the Day: TrkB
Boulle F, Kenis G, Cazorla M, Hamon M, Steinbusch HH, Lanfumey L, A van den Hove DL. TrkB inhibition as a therapeutic target for CNS-related disorders.Prog Neurobiol. 2012 Jun 12. [Epub ahead of print]
Abstract
The interaction of brain-derived neurotrophic factor (BDNF) with its tropomyosin-related kinase receptor B (TrkB) is involved in fundamental cellular processes including neuronal proliferation, differentiation and survival as well as neurotransmitter release and synaptic plasticity. TrkB signaling has been widely associated with beneficial, trophic effects and many commonly used psychotropic drugs aim to increase BDNF levels in the brain. However, it is likely that a prolonged increased TrkB activation is observed in many pathological conditions, which may underlie the development and course of clinical symptoms. Interestingly, genetic and pharmacological studies aiming at decreasing TrkB activation in rodent models mimicking human pathology have demonstrated a promising therapeutic landscape for TrkB inhibitors in the treatment of various diseases, e.g. central nervous system (CNS) disorders and several types of cancer. Up to date, only a few selective and potent TrkB inhibitors have been developed. As such, the use of crystallography and in silico approaches to model BDNF-TrkB interaction and to generate relevant pharmacophores represents powerful tools to develop novel compounds targeting the TrkB receptor.
Copyright © 2012. Published by Elsevier Ltd.
PMID: 22705453 [PubMed - as supplied by publisher]
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