Small molecules activating TrkB receptor for treating a variety of CNS disorders

Yan Zeng, Xiaonan Wang, Qiang Wang, Shumin Liu, Xiamin Hu, Shawn M. Mcclintock

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1066-1077
Number of pages12
JournalCNS and Neurological Disorders - Drug Targets
Volume12
Issue number7
DOIs
StatePublished - Nov 1 2013

Fingerprint

Brain-Derived Neurotrophic Factor
Adenosine A2 Receptor Agonists
Pharmacokinetics
Central Nervous System Diseases
Synapses
tropomyosin kinase
Therapeutics
Research

Keywords

  • Alzheimer's disease
  • Brain-derived neurotrophic factor
  • Cns disorders
  • Depression
  • Learning and memory
  • Mimetics
  • Small molecule
  • Synaptic plasticity
  • Tropomyosin-receptor-kinase b

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Cite this

Small molecules activating TrkB receptor for treating a variety of CNS disorders. / Zeng, Yan; Wang, Xiaonan; Wang, Qiang; Liu, Shumin; Hu, Xiamin; Mcclintock, Shawn M.

In: CNS and Neurological Disorders - Drug Targets, Vol. 12, No. 7, 01.11.2013, p. 1066-1077.

Research output: Contribution to journalArticle

Zeng, Yan ; Wang, Xiaonan ; Wang, Qiang ; Liu, Shumin ; Hu, Xiamin ; Mcclintock, Shawn M. / Small molecules activating TrkB receptor for treating a variety of CNS disorders. In: CNS and Neurological Disorders - Drug Targets. 2013 ; Vol. 12, No. 7. pp. 1066-1077.
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