A humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic mice.
A humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic mice.
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DOI：
10.1371/journal.pone.0016259
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发表时间：
2011-01-17
期刊：
影响因子：
3.7
通讯作者：
Matsuoka Y
中科院分区：
文献类型：
--
作者：
Niikura T;Sidahmed E;Hirata-Fukae C;Aisen PS;Matsuoka Y
护脑素 (HN) 是一种 24 残基肽，被鉴定为一种新型神经保护因子，在体外对多种阿尔茨海默病 (AD) 相关细胞毒性（包括暴露于β淀粉样蛋白 (Abeta) 下）表现出抗细胞死亡活性。我们之前证明，在 Abeta 注射小鼠模型中，将 S14G-HN（一种高效 HN 衍生物）注射到大脑中可以改善记忆丧失。为了充分了解 HN 在 AD 相关病理条件下的功能，我们检查了 S14G-HN 对携带 APPswe、tauP310L 和 PS-1M146V 的三重转基因小鼠的影响，这些小鼠显示与 AD 相关的多种病理的年龄依赖性发展。经过 3 个月的鼻内治疗后，行为分析表明 S14G-HN 改善了雄性小鼠的认知障碍。此外，ELISA 和免疫组织化学分析表明，S14G-HN 处理的雄性和雌性小鼠脑中 Abeta 水平显着低于载体对照小鼠。我们还发现，在 S14G-HN 处理的小鼠大脑中，海马结构外分子层中脑啡肽酶（一种 Abeta 降解酶）的表达水平有所增加。体外 S14G-HN 处理也提高了 NEP 活性。这些发现表明这些小鼠中 Abeta 水平的降低至少部分归因于 S14G-HN 诱导的脑啡肽酶水平的增加。尽管 HN 被确定为抗神经元死亡因子，但这些结果表明 HN 也可能对 AD 中淀粉样蛋白的积累具有治疗作用。
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 neprilysin, an Abeta degrading enzyme, in the outer molecular layer of hippocampal formation was increased in S14G-HN-treated mouse brains. NEP activity was also elevated by S14G-HN treatment in vitro. These findings suggest that decreased Abeta level in these mice is at least partly attributed to S14G-HN-induced increase of neprilysin level. Although HN was identified as an anti-neuronal death factor, these results indicate that HN may also have a therapeutic effect on amyloid accumulation in AD.
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影响因子：
2.7
作者：
Dix, SL;Aggleton, JP
通讯作者：
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影响因子：
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发表时间：
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