科研之友
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摘要
Aims: We previously reported that the neurotoxicity of amyloid beta protein (A beta(1-42), 10 nM) was blocked by an A beta-derived tripeptide, A beta(32-34) (Ile-Gly-Leu, IGL), suggesting that IGL may be a lead compound in the design of A beta antagonists. In the present Study. three stable forms of IGL peptide with acetylation of its N-terminal and/or amidation of its C-terminal (acetyl-IGL, IGL-NH2 and acetyl-IGL-NH2) were synthesized and examined for their effects on A beta-induced neurotoxicity. Main methods: Phosphatidylinositol 4-kinase type II (P14KII) activity was measured using recombinant human P14KII alpha kinase and cell viability was assessed in primary cultured hippocampal neurons. To test effects in vivo, 1.5 mu l of 100 nM A beta and/or 100 nM acetyl-IGL was injected into the hippocampal CA1 region of right hemisphere in transgenic mice expressing V337M human tau protein. Four weeks later, behavior performance in the Morris water maze was tested and after another 2 weeks, sections of brain were prepared for immunohistochemistry. Keyfindings: Among the three modified tripeptides, acetyl-IGL attenuated the A beta-incluced inhibition of P14KII activity as well as enhancement of glutamate neurotoxicity in primary cultured rat hippocampal neurons. Injection of A beta into the hippocampus of mice impaired spatial memory and increased the number of degenerating neurons in bilateral hippocampal regions. Co-injection of acetyl-IGL prevented the learning impairment as well as the neuronal degeneration induced by A beta. Significance: These results suggest that a modified tripeptide, acetyl-IGL, may be effective in the treatment of Alzheimer's disease.
- 出版日期2009-1-30
- 单位贵州医科大学
