PMID- 26740873
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160107
LR  - 20181113
IS  - 2047-9158 (Print)
IS  - 2047-9158 (Electronic)
IS  - 2047-9158 (Linking)
VI  - 5
DP  - 2016
TI  - 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating 
      various BDNF-implicated human disorders.
PG  - 2
LID - 10.1186/s40035-015-0048-7 [doi]
LID - 2
AB  - Brain-derived neurotrophic factor (BDNF) regulates a variety of biological 
      processes predominantly via binding to the transmembrane receptor tyrosine kinase 
      TrkB. It is a potential therapeutic target in numerous neurological, mental and 
      metabolic disorders. However, the lack of efficient means to deliver BDNF into 
      the body imposes an insurmountable hurdle to its clinical application. To address 
      this challenge, we initiated a cell-based drug screening to search for small 
      molecules that act as the TrkB agonist. 7,8-Dihydroxyflavone (7,8-DHF) is our 
      first reported small molecular TrkB agonist, which has now been extensively 
      validated in various biochemical and cellular systems. Though binding to the 
      extracellular domain of TrkB, 7,8-DHF triggers TrkB dimerization to induce the 
      downstream signaling. Notably, 7,8-DHF is orally bioactive that can penetrate the 
      brain blood barrier (BBB) to exert its neurotrophic activities in the central 
      nervous system. Numerous reports suggest 7,8-DHF processes promising therapeutic 
      efficacy in various animal disease models that are related to deficient BDNF 
      signaling. In this review, we summarize our current knowledge on the binding 
      activity and specificity, structure-activity relationship, pharmacokinetic and 
      metabolism, and the pre-clinical efficacy of 7,8-DHF against some human diseases.
FAU - Liu, Chaoyang
AU  - Liu C
AD  - School of Information and Safety Engineering, Zhongnan University of Economics 
      and Law, Wuhan, 430073 P.R. China.
FAU - Chan, Chi Bun
AU  - Chan CB
AD  - Department of Physiology, University of Oklahoma Health Sciences Center, 940 
      Stanton L. Young Blvd., Oklahoma City, OK 73104 USA.
FAU - Ye, Keqiang
AU  - Ye K
AD  - Department of Pathology and Laboratory Medicine, Emory University School of 
      Medicine, 615 Michael Street, Atlanta, GA 30322 USA.
LA  - eng
GR  - R01 NS045627/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20160106
PL  - England
TA  - Transl Neurodegener
JT  - Translational neurodegeneration
JID - 101591861
PMC - PMC4702337
OTO - NOTNLM
OT  - BDNF
OT  - Flavonoids
OT  - Mimetic compound
OT  - Neurotrophin
OT  - Receptor agonistic activity
EDAT- 2016/01/08 06:00
MHDA- 2016/01/08 06:01
PMCR- 2016/01/06
CRDT- 2016/01/08 06:00
PHST- 2015/09/30 00:00 [received]
PHST- 2015/12/29 00:00 [accepted]
PHST- 2016/01/08 06:00 [entrez]
PHST- 2016/01/08 06:00 [pubmed]
PHST- 2016/01/08 06:01 [medline]
PHST- 2016/01/06 00:00 [pmc-release]
AID - 48 [pii]
AID - 10.1186/s40035-015-0048-7 [doi]
PST - epublish
SO  - Transl Neurodegener. 2016 Jan 6;5:2. doi: 10.1186/s40035-015-0048-7. eCollection 
      2016.