FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.
FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.
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DOI：
10.1371/journal.pone.0027762
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Mobbs C
中科院分区：
文献类型：
--
作者：
Lublin A;Isoda F;Patel H;Yen K;Nguyen L;Hajje D;Schwartz M;Mobbs C
筛选一个已知对人体安全性的药物库，产生了30种可靠地保护哺乳动物神经元免受葡萄糖毒性的药物。随后的筛选表明，这30种药物中有6种可以延长C。咖啡因、环吡酮胺、单宁酸、对乙酰氨基酚、杆菌肽和黄芩素。每种药物都显著降低了死亡率的年龄依赖性加速。这些保护作用仅在成年人中被cbp-1的RNAi抑制所阻断，这也阻断了饮食限制的保护作用。只有两种药物，咖啡因和鞣酸，表现出类似的依赖性，对β-16。咖啡因、鞣酸和杆菌肽也减少了与阿尔茨海默病相关的蛋白毒性转基因模型的病理学。这些结果进一步支持葡萄糖毒性在驱动年龄相关病理学中的关键作用，以及CBP-1在保护免受年龄相关病理学中的关键作用。这些结果还提供了用于治疗年龄相关疾病（包括阿尔茨海默病和糖尿病并发症）的具有已知人体安全性特征的新型先导化合物。
Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications.
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影响因子：
3.6
作者：
Cui, Lili;Zhang, Xiangjian;Du, Wei
通讯作者：
Du, Wei
影响因子：
56.9
作者：
JOHNSON, TE
通讯作者：
JOHNSON, TE
影响因子：
64.8
作者：
Bishop, Nicholas A.;Guarente, Leonard
通讯作者：
Guarente, Leonard
DOI：
10.1073/pnas.92.20.9368
发表时间：
1995-09-26
影响因子：
11.1
作者：
LINK, CD
通讯作者：
LINK, CD
影响因子：
29
作者：
Lee SJ;Murphy CT;Kenyon C
通讯作者：
Kenyon C