title: Neurotrophic effects of amyloid precursor protein peptide 165 in vitro.
abstract: Diabetic encephalopathy is one of the risk factors for Alzheimer's disease. Our previous findings indicated that animals with diabetic encephalopathy exhibit learning and memory impairment in addition to hippocampal neurodegeneration, both of which are ameliorated with amyloid precursor protein (APP) 17-mer (APP17) peptide treatment. Although APP17 is neuroprotective, it is susceptible to enzymatic degradation. Derived from the active sequence structure of APP17, we have previously structurally transformed and modified several APP5-mer peptides (APP328-332 [RERMS], APP 5). We have developed seven different derivatives of APP5, including several analogs. Results from the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on human neuroblastoma SH-SY5Y cells in the present study showed that P165 was the most neuroprotective APP5 derivative. Furthermore, we tested the effects of APP5 and P165 on the number of cells and the release of lactate dehydrogenase. Western immunoblot analyses were also performed. The digestion rates of P165 and APP5 were determined by the pepsin digestion test. P165 resisted pepsin digestion significantly more than APP5. Therefore, P165 may be optimal for oral administration. Overall, these findings suggest that P165 may be a potential drug for the treatment of diabetic encephalopathy.
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing 100053, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yao
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing 100053, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Ma
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing 100053, China. Electronic address: rong_wang72@aliyun.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing 100053, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Sheng
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing 100053, China.
authors.forename: Zhijuan
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Central Laboratory, Xuan Wu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing 100053, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D016564:Amyloid beta-Protein Precursor / Q000493:pharmacokinetics / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D010434:Pepsin A / Q000378:metabolism; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: C000602555:APP5-mer peptide; D016564:Amyloid beta-Protein Precursor; C000595707:BCL2 protein, human; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D007770:L-Lactate Dehydrogenase; D010434:Pepsin A
keywords: Diabetic encephalopathy; Neurotrophy; Pepsin digestion; Peptide 165