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THE N-TERMINAL 5-MER PEPTIDE ANALOGUE P165 OF AMYLOID PRECURSOR PROTEIN EXERTS PROTECTIVE EFFECTS ON SH-SY5Y CELLS AND RAT HIPPOCAMPUS NEURONAL SYNAPSES

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收录情况： ◇ SCIE

作者：
P. WANG,[a,b] * ; S. JIANG[c] ; Y. CUI,[d] ; Z. YUE,[e] ; C. SU,[c] ; J. SUN,[b] ; S. SHENG[f] ; J. TIAN[a,g,*] ;
机构： [a]Key Laboratory of Chinese Internal Medicine (Beijing University of Chinese Medicine), Ministry of Education, Beijing, 100700, People’s Republic of China [b]Key Laboratory of Pharmacology of Chinese Materia Medica (Beijing University of Chinese Medicine), State Administration of Traditional Chinese Medicine, Beijing, 100102, People’s Republic of China [c]Department of Surgery (Neurobiology) and Hamilton Neuro Restorative Group, McMaster University, Health Sciences Centre, Room 4E15, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada [d]Department of Pathology, Beijing Joinn Laboratory, Beijing, 100176, People’s Republic of China [e]Department of Hematology Center, Beijing Children’s Hospital Affiliated to Capital Medical University, Beijing, 100045, People’s Republic of China [f]Central Laboratory, Xuanwu Hospital, Capital Medical University, Beijing, 100054, People’s Republic of China [g]Beijing University of Chinese Medicine, Neurology Center, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China
出处：
DOI： 10.1016/j.neuroscience.2010.10.069
ISSN：

关键词： streptozotocin Alzheimer's disease immunohistochemistry western blot insulin signaling pathway

摘要：
The disturbance of the insulin-signaling pathway plays an important role in Alzheimer's disease. Resistance to insulin signaling renders neurons energy-deficient and vulnerable to oxidization or other metabolic insults and impairs synaptic plasticity. In search of neuroprotective drugs, we synthesized a peptide analogue, P165, an active domain of the soluble amyloid precursor protein, which is resistant to degradation and is suitable for oral administration in a clinical setting. Initially, we confirmed that P165 can protect cells from streptozotocin-caused damage and stimulate cell outgrowth using cultured SH-SY5Y cell lines treated with streptozotocin. P165 significantly reduced lactate dehydrogenase leakage from damaged cells, thereby rescuing cell energy production. Insulin signaling such as insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) proteins were upregulated to stimulate cell survival and growth. We proceeded to investigate the effect of P165 on streptozotocin-treated Alzheimer's disease (AD) rats. The data showed that P165 protected synaptic loss and dysfunction by increasing synaptophysin and PSD-95 (post synaptic density95), while simultaneously decreasing a-synuclein expression. Moreover, animal behavior testing clearly showed that P165 increased rats' learning and memory activity. Overall, these results constitute evidence that peptide analogue 165 may protect synapse and improve learning and memory ability in AD. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

基金：
Beijing Natural Science Foundation (No. 7092057), the 111 Project (B08006) and IRT (0810).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2010]版：
大类 | 2 区 医学
小类 | 3 区 神经科学
最新[2023]版：
大类 | 3 区 医学
小类 | 4 区 神经科学
JCR分区：
出版当年[2009]版：
Q2 NEUROSCIENCES
最新[2023]版：
Q2 NEUROSCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2009版] 出版当年五年平均 出版前一年[2008版] 出版后一年[2010版]

第一作者：
第一作者机构： [a]Key Laboratory of Chinese Internal Medicine (Beijing University of Chinese Medicine), Ministry of Education, Beijing, 100700, People’s Republic of China [b]Key Laboratory of Pharmacology of Chinese Materia Medica (Beijing University of Chinese Medicine), State Administration of Traditional Chinese Medicine, Beijing, 100102, People’s Republic of China
通讯作者：
通讯机构： [*]Key Laboratory of Chinese Internal Medicine (Beijing University of Chinese Medicine), Ministry of Education, Beijing, 100700, People’s Republic of China
推荐引用方式(GB/T 7714)：
P. WANG ,S. JIANG,Y. CUI ,et al.THE N-TERMINAL 5-MER PEPTIDE ANALOGUE P165 OF AMYLOID PRECURSOR PROTEIN EXERTS PROTECTIVE EFFECTS ON SH-SY5Y CELLS AND RAT HIPPOCAMPUS NEURONAL SYNAPSES[J].NEUROSCIENCE.2011,173:169-178.doi:10.1016/j.neuroscience.2010.10.069.
APA：
P. WANG,,S. JIANG,Y. CUI,,Z. YUE,,C. SU,...&J. TIAN.(2011).THE N-TERMINAL 5-MER PEPTIDE ANALOGUE P165 OF AMYLOID PRECURSOR PROTEIN EXERTS PROTECTIVE EFFECTS ON SH-SY5Y CELLS AND RAT HIPPOCAMPUS NEURONAL SYNAPSES.NEUROSCIENCE,173,
MLA：
P. WANG,,et al."THE N-TERMINAL 5-MER PEPTIDE ANALOGUE P165 OF AMYLOID PRECURSOR PROTEIN EXERTS PROTECTIVE EFFECTS ON SH-SY5Y CELLS AND RAT HIPPOCAMPUS NEURONAL SYNAPSES".NEUROSCIENCE 173.(2011):169-178

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