title: Effects of APP 5-mer peptide analogue P165 on the synaptic proteins and insulin signal transduction proteins.
abstract: 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 Aβ25-35 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 α-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.
authors.affiliation: Department of Neurology, Provincial Hospital Affiliated to Shandong University 324 Jingwu Road, Jinan, Shandong 250021, China ; Department of Neurology, Hospital Affiliated to Binzhou Medical University 661 Second Huanghe Street, Binzhou 256603, China ; Department of Spine, Hospital Affiliated to Binzhou Medical University 661 Second Huanghe Street, Binzhou 256603, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Spine, Hospital Affiliated to Binzhou Medical University 661 Second Huanghe Street, Binzhou 256603, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.affiliation: Department of Neurology, Hospital Affiliated to Binzhou Medical University 661 Second Huanghe Street, Binzhou 256603, China.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Lu
authors.affiliation: Central Laboratory, Xuanwu Hospital, Capital Medical University 45 Changchun Street, Beijing 100053, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurology, Provincial Hospital Affiliated to Shandong University 324 Jingwu Road, Jinan, Shandong 250021, China.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Du
keywords: APP 5-mer peptide analogue P165; Alzheimer’s disease; diabetes mellitus; insulin signal transduction; synapse
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