PMID- 26262618
OWN - NLM
STAT- MEDLINE
DCOM- 20160509
LR  - 20181113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 16
IP  - 8
DP  - 2015 Aug 7
TI  - SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances 
      CREB/BDNF/TrkB Signaling without Affecting Abeta Burden in AbetaPP/PS1 Mice.
PG  - 18544-63
LID - 10.3390/ijms160818544 [doi]
AB  - SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to 
      possess considerable neuroprotective effects in animal models of ischemic stroke, 
      Parkinson's disease and Alzheimer's disease (AD). In this study, we demonstrated 
      for the first time that 3-month oral SCM-198 treatment could significantly 
      improve both recognition and spatial memory, inhibit microgliosis and promote 
      neuronal survival in amyloid-beta protein precursor and presenilin-1(AbetaPP/PS1) 
      double-transgenic mice without affecting amyloid-beta (Abeta) burden. In addition, 
      decreases in cAMP-response element-binding protein (CREB) phosphorylation, 
      brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) 
      phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical 
      neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting 
      the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by 
      SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal 
      survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on 
      behavioral and biochemical alterations without affecting Abeta burden in AbetaPP/PS1 
      mice and might become a potential drug candidate for AD treatment in the future.
FAU - Hong, Zhen-Yi
AU  - Hong ZY
AD  - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, 
      School of Pharmacy, Fudan University, Shanghai 201203, China. cerulian@163.com.
FAU - Yu, Shuang-Shuang
AU  - Yu SS
AD  - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, 
      School of Pharmacy, Fudan University, Shanghai 201203, China. yss2359450@163.com.
FAU - Wang, Zhi-Jun
AU  - Wang ZJ
AD  - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, 
      School of Pharmacy, Fudan University, Shanghai 201203, China. oscarwzj@gmail.com.
FAU - Zhu, Yi-Zhun
AU  - Zhu YZ
AD  - Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, 
      School of Pharmacy, Fudan University, Shanghai 201203, China. 
      yizhunzhu@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150807
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neuroprotective Agents)
RN  - 09Q5W34QDA (leonurine)
RN  - 632XD903SP (Gallic Acid)
RN  - EC 2.7.10.1 (Ntrk2 protein, mouse)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Brain/*drug effects/metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cognition Disorders/*drug therapy/metabolism/physiopathology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Gallic Acid/*analogs & derivatives/therapeutic use
MH  - Humans
MH  - Male
MH  - Maze Learning/drug effects
MH  - Membrane Glycoproteins/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Neurons/cytology/drug effects/metabolism/pathology
MH  - Neuroprotective Agents/*therapeutic use
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Signal Transduction/*drug effects
PMC - PMC4581259
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Morris water maze
OT  - SCM-198
OT  - amyloid-beta
OT  - brain-derived neurotrophic factor
OT  - cAMP-responsive element-binding protein
OT  - novel object recognition
OT  - tropomyosin-related kinase B
EDAT- 2015/08/12 06:00
MHDA- 2016/05/10 06:00
PMCR- 2015/08/01
CRDT- 2015/08/12 06:00
PHST- 2015/06/15 00:00 [received]
PHST- 2015/07/29 00:00 [revised]
PHST- 2015/07/31 00:00 [accepted]
PHST- 2015/08/12 06:00 [entrez]
PHST- 2015/08/12 06:00 [pubmed]
PHST- 2016/05/10 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - ijms160818544 [pii]
AID - ijms-16-18544 [pii]
AID - 10.3390/ijms160818544 [doi]
PST - epublish
SO  - Int J Mol Sci. 2015 Aug 7;16(8):18544-63. doi: 10.3390/ijms160818544.