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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.
AuthorsJie Yao, Lina Ma, Rong Wang, Shuli Sheng, Zhijuan Ji, Jingyan Zhang
JournalBrain research bulletin (Brain Res Bull) Vol. 120 Pg. 58-62 (Jan 2016) ISSN: 1873-2747 [Electronic] United States
PMID26551064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • APP5-mer peptide
  • Amyloid beta-Protein Precursor
  • BCL2 protein, human
  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Neuroprotective Agents
  • Peptide Fragments
  • Proto-Oncogene Proteins c-bcl-2
  • L-Lactate Dehydrogenase
  • Pepsin A
Topics
  • Administration, Oral
  • Amyloid beta-Protein Precursor (pharmacokinetics, pharmacology)
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival (drug effects, physiology)
  • Chromatography, High Pressure Liquid
  • Cyclic AMP Response Element-Binding Protein (metabolism)
  • Humans
  • L-Lactate Dehydrogenase (metabolism)
  • Neurons (drug effects, physiology)
  • Neuroprotective Agents (pharmacokinetics, pharmacology)
  • Pepsin A (metabolism)
  • Peptide Fragments (pharmacokinetics, pharmacology)
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2 (metabolism)

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