PMID- 23844685
OWN - NLM
STAT- MEDLINE
DCOM- 20141112
LR  - 20191027
IS  - 1996-3181 (Electronic)
IS  - 1871-5273 (Linking)
VI  - 12
IP  - 7
DP  - 2013 Nov
TI  - Small molecules activating TrkB receptor for treating a variety of CNS disorders.
PG  - 1066-77
AB  - 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.
FAU - Zeng, Yan
AU  - Zeng Y
AD  - Department of Pathophysiology, School of Medicine, Wuhan University of Science 
      and Technology, Wuhan 430065, China. yanzeng11@yahoo.com.
FAU - Wang, Xiaonan
AU  - Wang X
FAU - Wang, Qiang
AU  - Wang Q
FAU - Liu, Shumin
AU  - Liu S
FAU - Hu, Xiamin
AU  - Hu X
FAU - McClintock, Shawn M
AU  - McClintock SM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United Arab Emirates
TA  - CNS Neurol Disord Drug Targets
JT  - CNS & neurological disorders drug targets
JID - 101269155
RN  - 0 (6,7-dihydroxyflavone)
RN  - 0 (Adenosine A2 Receptor Agonists)
RN  - 0 (Flavones)
RN  - 0 (Peptidomimetics)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Adenosine A2 Receptor Agonists/*therapeutic use
MH  - Animals
MH  - Central Nervous System Diseases/*drug therapy
MH  - Flavones/pharmacology/*therapeutic use
MH  - Humans
MH  - *Molecular Targeted Therapy
MH  - Peptidomimetics/pharmacology/*therapeutic use
MH  - Receptor, trkB/*agonists
MH  - Signal Transduction/drug effects
EDAT- 2013/07/13 06:00
MHDA- 2014/11/13 06:00
CRDT- 2013/07/13 06:00
PHST- 2013/02/08 00:00 [received]
PHST- 2013/05/28 00:00 [revised]
PHST- 2013/06/07 00:00 [accepted]
PHST- 2013/07/13 06:00 [entrez]
PHST- 2013/07/13 06:00 [pubmed]
PHST- 2014/11/13 06:00 [medline]
AID - CNSNDDT-EPUB-53932 [pii]
AID - 10.2174/18715273113129990089 [doi]
PST - ppublish
SO  - CNS Neurol Disord Drug Targets. 2013 Nov;12(7):1066-77. doi: 
      10.2174/18715273113129990089.