Abstract
The brain-derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin-receptor-kinase B (TrkB) play a critical role in neuronal differentiation and survival, synapse plasticity, and memory. Indeed, both have been implicated in the pathophysiology of numerous diseases. Although the remarkable therapeutic potential of BDNF has generated much research over the past decade, the poor pharmacokinetics and adverse side effect profile have limited its clinical usefulness of BDNF. Small compounds that mimic BDNF’s neurotrophic signaling and overcome the pharmacokinetic and side effect barriers may have greater therapeutic potential. The purpose of this review is to provide a survey of the various strategies taken towards the development of small molecule mimetics for BDNF and the selective TrkB agonist. A particular focus was placed on TrkB agonist 7, 8-dihydroxyflavone, which modulates multiple functions and has demonstrated remarkable therapeutic efficacy in a variety of central nervous system disease models. Two other small molecules included in this review are adenosine A2A receptor agonists that indirectly activate TrkB, and TrkB binding domains of BDNF, loop II-LM22A compounds that directly activate TrkB. These alternative molecules have shown promise in preclinical studies and may be included in prospective clinical investigations.
Keywords: Brain-derived neurotrophic factor, small molecule, Alzheimer’s disease, tropomyosin-receptor-kinase B, mimetics, CNS disorders, synaptic plasticity, learning and memory, depression.
CNS & Neurological Disorders - Drug Targets
Title:Small Molecules Activating TrkB Receptor for Treating a Variety of CNS Disorders
Volume: 12 Issue: 7
Author(s): Yan Zeng, Xiaonan Wang, Qiang Wang, Shumin Liu, Xiamin Hu and Shawn M. McClintock
Affiliation:
Keywords: Brain-derived neurotrophic factor, small molecule, Alzheimer’s disease, tropomyosin-receptor-kinase B, mimetics, CNS disorders, synaptic plasticity, learning and memory, depression.
Abstract: The brain-derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin-receptor-kinase B (TrkB) play a critical role in neuronal differentiation and survival, synapse plasticity, and memory. Indeed, both have been implicated in the pathophysiology of numerous diseases. Although the remarkable therapeutic potential of BDNF has generated much research over the past decade, the poor pharmacokinetics and adverse side effect profile have limited its clinical usefulness of BDNF. Small compounds that mimic BDNF’s neurotrophic signaling and overcome the pharmacokinetic and side effect barriers may have greater therapeutic potential. The purpose of this review is to provide a survey of the various strategies taken towards the development of small molecule mimetics for BDNF and the selective TrkB agonist. A particular focus was placed on TrkB agonist 7, 8-dihydroxyflavone, which modulates multiple functions and has demonstrated remarkable therapeutic efficacy in a variety of central nervous system disease models. Two other small molecules included in this review are adenosine A2A receptor agonists that indirectly activate TrkB, and TrkB binding domains of BDNF, loop II-LM22A compounds that directly activate TrkB. These alternative molecules have shown promise in preclinical studies and may be included in prospective clinical investigations.
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Cite this article as:
Zeng Yan, Wang Xiaonan, Wang Qiang, Liu Shumin, Hu Xiamin and McClintock M. Shawn, Small Molecules Activating TrkB Receptor for Treating a Variety of CNS Disorders, CNS & Neurological Disorders - Drug Targets 2013; 12 (7) . https://dx.doi.org/10.2174/18715273113129990089
DOI https://dx.doi.org/10.2174/18715273113129990089 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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