PMID- 20154710
OWN - NLM
STAT- MEDLINE
DCOM- 20100614
LR  - 20220316
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 31
IP  - 3
DP  - 2010 Mar
TI  - The novel squamosamide derivative FLZ enhances BDNF/TrkB/CREB signaling and 
      inhibits neuronal apoptosis in APP/PS1 mice.
PG  - 265-72
LID - 10.1038/aps.2010.3 [doi]
AB  - AIM: The aim of this study was to study the effects of compound FLZ, a novel 
      cyclic derivative of squamosamide from Annona glabra, on brain-derived 
      neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response 
      element-binding protein (CREB) signaling and neuronal apoptosis in the 
      hippocampus of the amyloid precursor protein (APP)/presenilin-1 (PS1) double 
      transgenic mice. METHODS: APP/PS1 mice at the age of 5 months and age-matched 
      wild-type mice (WT) were intragastrically administered FLZ (150 mg/kg) or vehicle 
      [0.05% carboxymethyl cellulose sodium (CMC-Na)] daily for 20 weeks. The levels of 
      BDNF in the hippocampus of WT and APP/PS1 mice were then measured by 
      immunohistochemistry and Western blot analysis. Neuronal apoptosis in mouse 
      hippocampus was detected by Nissl staining. Expression of NGF, NT3, pTrkB 
      (Tyr515)/TrkB, pAkt (Ser473)/Akt, pERK/ERK, pCREB (Ser133)/CREB, Bcl-2/Bax, and 
      active caspase-3 fragment/caspase-3 in the hippocampus of WT and APP/PS1 mice was 
      detected by Western blot analysis. RESULTS: Compared with vehicle-treated APP/PS1 
      mice, FLZ (150 mg/kg) significantly increased BDNF and NT3 expression in the 
      hippocampus of APP/PS1 mice. In addition, FLZ promoted BDNF high-affinity 
      receptor TrkB phosphorylation and activated its downstream ERK, thus increasing 
      phosphorylation of CREB at Ser133 in the hippocampus of APP/PS1 mice. Moreover, 
      FLZ showed neuroprotective effects on neuronal apoptosis by increasing the 
      Bcl-2/Bax ratio and decreasing the active caspase-3 fragment/caspase-3 ratio in 
      the hippocampus of APP/PS1 mice. CONCLUSION: FLZ exerted neuroprotection at least 
      partly through enhancing the BDNF/TrkB/CREB pathway and inhibiting neuronal 
      apoptosis in APP/PS1 mice, which suggests that FLZ can be explored as a potential 
      therapeutic agent in long-term Alzheimer's disease therapy.
FAU - Li, Ning
AU  - Li N
AD  - Department of Pharmacology, Institute of Materia Medica, Peking Union Medical 
      College and Chinese Academy of Medical Sciences, Beijing, China.
FAU - Liu, Geng-tao
AU  - Liu GT
LA  - eng
PT  - Journal Article
DEP - 20100215
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Benzeneacetamides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Phenols)
RN  - 0 (Presenilin-1)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 142750-35-4 (squamosamide)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Alzheimer Disease/*drug therapy
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Benzeneacetamides/*pharmacology/therapeutic use
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Caspase 3/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Female
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Neurons/cytology/drug effects
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Phenols/*pharmacology/therapeutic use
MH  - Presenilin-1/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Receptor, trkB/*metabolism
MH  - Signal Transduction/drug effects
MH  - bcl-2-Associated X Protein/metabolism
PMC - PMC4002416
EDAT- 2010/02/16 06:00
MHDA- 2010/06/15 06:00
PMCR- 2010/03/01
CRDT- 2010/02/16 06:00
PHST- 2010/02/16 06:00 [entrez]
PHST- 2010/02/16 06:00 [pubmed]
PHST- 2010/06/15 06:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - aps20103 [pii]
AID - 10.1038/aps.2010.3 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2010 Mar;31(3):265-72. doi: 10.1038/aps.2010.3. Epub 2010 Feb 
      15.