a humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic micehumanin导数减少β淀粉样蛋白的积累和改善内存赤字三重转基因老鼠.pdfVIP

a humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic micehumanin导数减少β淀粉样蛋白的积累和改善内存赤字三重转基因老鼠.pdf

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a humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic micehumanin导数减少β淀粉样蛋白的积累和改善内存赤字三重转基因老鼠

A Humanin Derivative Reduces Amyloid Beta Accumulation and Ameliorates Memory Deficit in Triple Transgenic Mice 1,2 2 2 3 2¤ Takako Niikura *, Elkhansa Sidahmed , Chiho Hirata-Fukae , Paul S. Aisen , Yasuji Matsuoka 1 Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada, 2 Department of Neurology, Georgetown University, Washington, D. C., United States of America, 3 Department of Neurosciences, University of California San Diego, La Jolla, California, United States of America Abstract Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer’s disease (AD)-related cytotoxicities, including exposure to amyloid beta (Abeta), in vitro. We previously demonstrated that the injection of S14G-HN, a highly potent HN derivative, into brain ameliorated memory loss in an Abeta-injection mouse model. To fully understand HN’s functions under AD-associated pathological conditions, we examined the effect of S14G-HN on triple transgenic mice harboring APPswe, tauP310L, and PS-1M146V that show the age-dependent development of multiple pathologies relating to AD. After 3 months of intranasal treatment, behavioral analyses showed that S14G-HN ameliorated cognitive impairment in male mice. Moreover, ELISA and immunohistochemical analyses showed that Abeta levels in brains were markedly lower in S14G-HN-treated male and female mice than in vehicle control mice. We also found the expression level of n

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