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Effects of APP 5-mer peptide analogue P165 on the synaptic proteins and insulin signal transduction proteins

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机构: [1]Department of Neurology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, China [2]Department of Neurology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603, China [3]Department of Spine, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603, China [4]Central Laboratory, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, China
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关键词: Alzheimer's disease APP 5-mer peptide analogue P165 diabetes mellitus insulin signal transduction synapse

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Diabetic encephalopathy (DE) is one of risk factors for Alzheimer's disease (AD). Our previous findings indicated that DE animals had impairment of learning and memory and degeneration of hippocampal neurons, which could be improved by neurotrophic peptide. APP 17-mer peptide is a synthesized peptide sequenced from soluble amyloid precursor protein. APP 17-mer peptide has neural protective effect, but is susceptible to enzyme degradation. Soluble APP 5-mer peptide is the active form of APP 17-mer peptide, and composed of arginine, glutamic acid, arginine, methionine and serine. P165, an APP 5-mer peptide analog reconstructed by our lab, is resistant to enzyme degradation, and can be orally used to protect neurons. In the present study, high glucose and A beta(25-35) were used to cause injury to human neuroblastoma cell line SH-SY5Y in vitro, and streptozotocin was used to induce diabetes in mice in vivo. The changes in synaptic proteins and proteins of insulin signal transduction which closely correlate with learning and memory were detected in these cells and the brain of mice. Results showed that P165 could up-regulate the expression of alpha-synuclein and insulin receptor (IR), down-regulate the expression of insulin receptor substrate-1 (IRS-1), PSD-95, Shank1 and MAPK expression. All these findings suggest that nicorandil might be a potential drug used for the treatment of AD.

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Q4 MEDICINE, RESEARCH & EXPERIMENTAL

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第一作者机构: [1]Department of Neurology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, China [2]Department of Neurology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603, China [3]Department of Spine, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603, China
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通讯机构: [*1]Department of Neurology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, China. [*2]Central Laboratory, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053 China
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