Small-molecule Klotho enhancers as novel treatment of neurodegeneration.
Small-molecule Klotho enhancers as novel treatment of neurodegeneration.
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DOI：
10.4155/fmc.12.134
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发表时间：
2012-09
影响因子：
4.2
通讯作者：
Zeldich E
中科院分区：
文献类型：
--
作者：
Abraham CR;Chen C;Cuny GD;Glicksman MA;Zeldich E
大多数神经退行性疾病都有重要的年龄组成部分，因此，了解大脑正常衰老过程中发生的分子变化至关重要。为了寻找在人类、猴子和啮齿动物中发现的与年龄相关的认知能力下降的基础，我们研究了恒河猴。令人惊讶的是，老年猴子大脑中的神经元没有损失。然而，我们报告了老年猴子的白色物质和髓鞘异常，与在阿尔茨海默病和多发性硬化症患者中观察到的相似。在比较年轻和老年猴子白色物质的微阵列分析中，我们发现Klotho在老年大脑中下调。然后，我们询问年龄相关的认知能力下降，髓鞘异常和Klotho下调之间是否存在联系。如果发现这种联系，上调Klotho表达的化合物可能会成为治疗多发性硬化症，甚至阿尔茨海默病的治疗兴趣。
The majority of neurodegenerative diseases have an important age component, and thus, understanding the molecular changes that occur during normal aging of the brain is of utmost relevance. In search for the basis of the age-related cognitive decline found in humans, monkeys and rodents, we study the rhesus monkey. Surprisingly, there is no loss of neurons in aged monkey brains. However, we reported white matter and myelin abnormalities in aged monkeys, similar to those observed in Alzheimer’s disease and multiple sclerosis patients. In a microarray analysis comparing young and old monkey white matter, we discovered that Klotho is downregulated in the aged brain. We then asked whether there is a connection between the age-related cognitive decline, myelin abnormalities and Klotho downregulation. If such a connection is found, compounds that upregulate Klotho expression could become of therapeutic interest for the treatment of multiple sclerosis, and perhaps even Alzheimer’s disease.
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影响因子：
158.5
作者：
Chang, A;Tourtellotte, WW;Trapp, BD
通讯作者：
Trapp, BD
影响因子：
15.9
作者：
Ichikawa, Shoji;Lmel, Erik A.;Econs, Michael J.
通讯作者：
Econs, Michael J.
影响因子：
56.9
作者：
Kurosu, H;Yamamoto, M;Kuro-o, M
通讯作者：
Kuro-o, M
DOI：
10.3904/kjim.2011.26.2.113
发表时间：
2011-06
期刊：
The Korean journal of internal medicine
影响因子：
--
作者：
Kuro-o M
通讯作者：
Kuro-o M
影响因子：
21.3
作者：
Liu, Feng;Wu, Su;Gu, Jun
通讯作者：
Gu, Jun