PMID- 22441042
OWN - NLM
STAT- MEDLINE
DCOM- 20120921
LR  - 20121115
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 210
DP  - 2012 May 17
TI  - Smilagenin attenuates beta amyloid (25-35)-induced degeneration of neuronal cells 
      via stimulating the gene expression of brain-derived neurotrophic factor.
PG  - 275-85
LID - 10.1016/j.neuroscience.2012.03.017 [doi]
AB  - The development of drugs that attenuate neurodegeneration is important for the 
      treatment of Alzheimer's disease (AD). We previously found that smilagenin (SMI), 
      a steroidal sapogenin from traditional Chinese medicinal herbs improves memory in 
      animal models, is neither a cholinesterase inhibitor nor a glutamate receptor 
      antagonist, but can significantly elevate the declined muscarinic receptor (M 
      receptor) density. In this article, to clarify whether SMI represents a new 
      approach for treating neurodegeneration disease, we first demonstrate that SMI 
      pretreatment significantly attenuates the neurodegenerative changes induced by 
      beta amyloid 25-35 (Abeta(25-35)) in cultured rat cortical neurons, including 
      decreased cholinergic neuron number, shortened neurite outgrowth length, and 
      declined M receptor density. Brain-derived neurotrophic factor (BDNF) protein 
      levels in the culture medium were also decreased by Abeta(25-35) and significantly 
      elevated by SMI. Parallel experiments revealed that when the trk receptors were 
      inhibited by K252a or the action of BDNF was inhibited by a neutralizing 
      anti-BDNF antibody, the effects of SMI on the Abeta(25-35)-induced neurodegeneration 
      in rat cortical neurons were almost completely abolished. In the all-trans 
      retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cells, the BDNF 
      transcription rate measured by a nuclear run-on assay was significantly 
      suppressed by Abeta(25-35) and elevated by SMI, but the BDNF degradation rate 
      measured by half-life determination was unchanged by Abeta(25-35) and SMI. 
      Transcript analysis of the SH-SY5Y cells using quantitative RT-PCR (qRT-PCR) 
      showed that the IV and VI transcripts of BDNF mRNA were significantly decreased 
      by Abeta(25-35) and elevated by SMI. Taken together, we conclude that SMI attenuates 
      Abeta(25-35)-induced neurodegeneration in cultured rat cortical neurons and SH-SY5Y 
      cells mainly through stimulating BDNF mRNA transcription implicating that SMI may 
      represent a novel therapeutic strategy for AD.
CI  - Copyright (c) 2012 IBRO. All rights reserved.
FAU - Zhang, R
AU  - Zhang R
AD  - Research Laboratory of Cell Regulation, Shanghai Jiaotong University School of 
      Medicine, 280 South Chongqing Road, Shanghai 200025, China.
FAU - Wang, Z
AU  - Wang Z
FAU - Howson, P A
AU  - Howson PA
FAU - Xia, Z
AU  - Xia Z
FAU - Zhou, S
AU  - Zhou S
FAU - Wu, E
AU  - Wu E
FAU - Xia, Z
AU  - Xia Z
FAU - Hu, Y
AU  - Hu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120313
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Spirostans)
RN  - CFS802C28F (sarsasapogenin)
SB  - IM
MH  - Amyloid beta-Peptides/*toxicity
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Cell Line
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Nerve Degeneration/*metabolism
MH  - Neurons/*drug effects/metabolism
MH  - Rats
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Spirostans/*pharmacology
EDAT- 2012/03/24 06:00
MHDA- 2012/09/22 06:00
CRDT- 2012/03/24 06:00
PHST- 2012/03/02 00:00 [received]
PHST- 2012/03/06 00:00 [accepted]
PHST- 2012/03/24 06:00 [entrez]
PHST- 2012/03/24 06:00 [pubmed]
PHST- 2012/09/22 06:00 [medline]
AID - S0306-4522(12)00229-1 [pii]
AID - 10.1016/j.neuroscience.2012.03.017 [doi]
PST - ppublish
SO  - Neuroscience. 2012 May 17;210:275-85. doi: 10.1016/j.neuroscience.2012.03.017. 
      Epub 2012 Mar 13.