神经营养复合J147逆转年龄在阿尔茨海默病小鼠认知障碍。

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M之前,Dargusch R, Ehren杰,Chiruta C,舒伯特D

神经营养复合J147逆转年龄在阿尔茨海默病小鼠认知障碍。

老年痴呆症Res。2013年5月14日,5 (3):25。doi: 10.1186 / alzrt179。eCollection 2013。

PubMed ID

23673233 (在PubMed

]

文摘

作品简介:尽管经过多年的研究,没有疾病修饰药物阿尔茨海默病(AD),一个致命的,与年龄相关的神经退行性疾病。筛查潜在疗法在动物模型中广告通常依赖于测试化合物的病理存在之前,从而建模修改疾病预防,而不是疾病。此外,这种筛选方法不能反映AD病人的临床表现可以解释未能翻译化合物在动物模型中已经被认为是有益的对疾病的修改化合物在临床试验中。显然一个更好的方法为临床前药物筛选广告是必需的。方法:为了更准确地反映了临床,我们使用另一种筛选策略包括广告老鼠在一个阶段的治疗在疾病病理已经是先进的。岁(20个月大)转基因小鼠广告(APP / swePS1DeltaE9)美联储异常强大,口头活跃,记忆力增强和神经营养分子称为J147。认知行为化验、组织学、ELISA和免疫印迹分析J147对记忆的影响,淀粉样蛋白代谢和神经通路。J147也调查scopolamine-induced在C57Bl / 6 j小鼠记忆障碍模型和多奈哌齐相比。细节还包括J147的药理学和安全。结果:本文提供的数据表明,J147有能力拯救认知缺陷管理时的晚期疾病。 The ability of J147 to improve memory in aged AD mice is correlated with its induction of the neurotrophic factors NGF (nerve growth factor) and BDNF (brain derived neurotrophic factor) as well as several BDNF-responsive proteins which are important for learning and memory. The comparison between J147 and donepezil in the scopolamine model showed that while both compounds were comparable at rescuing short term memory, J147 was superior at rescuing spatial memory and a combination of the two worked best for contextual and cued memory. CONCLUSION: J147 is an exciting new compound that is extremely potent, safe in animal studies and orally active. J147 is a potential AD therapeutic due to its ability to provide immediate cognition benefits, and it also has the potential to halt and perhaps reverse disease progression in symptomatic animals as demonstrated in these studies.

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药物

J147