Reduced IGF-1 signaling delays age-associated proteotoxicity in mice.
Reduced IGF-1 signaling delays age-associated proteotoxicity in mice.
复制标题
IGF-1信号传导降低会延迟小鼠年龄相关的蛋白质毒性。
DOI：
10.1016/j.cell.2009.11.014
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发表时间：
2009-12-11
期刊：
影响因子：
64.5
通讯作者：
Dillin A
中科院分区：
文献类型：
--
作者：
Cohen E;Paulsson JF;Blinder P;Burstyn-Cohen T;Du D;Estepa G;Adame A;Pham HM;Holzenberger M;Kelly JW;Masliah E;Dillin A
胰岛素/IGF信号通路（IIS）是蠕虫、苍蝇、小鼠和可能的人类衰老的重要调节因子。IIS减少延缓衰老可以保护线虫免受与阿尔茨海默病相关的人类肽Aβ聚集相关的毒性。我们减少了阿尔茨海默氏症模型小鼠的IGF信号，发现这些动物免受阿尔茨海默氏症样疾病症状的影响，包括减少行为障碍、神经炎症、神经元和突触丧失。这种保护与Aβ的超聚集相关，导致紧密堆积，有序斑块，这表明IGF信号传导减少所赋予的保护的一个方面是可溶性Aβ低聚物可能被隔离成毒性较低的致密聚集体。这些发现表明，从蠕虫到哺乳动物，IGF信号调节机制对a β毒性的保护是保守的，并指出这一信号通路的调节是开发阿尔茨海默病治疗的一个有希望的策略。
The Insulin/IGF signaling pathway (IIS) is a prominent regulator of aging of worms, flies, mice and likely humans. Delayed aging by IIS reduction protects the nematode, C. elegans, from toxicity associated with the aggregation of the Alzheimer's disease linked human peptide, Aβ. We reduced IGF signaling in Alzheimer's model mice and discovered that these animals are protected from the Alzheimer's-like disease symptoms including reduced behavioral impairment, neruoinflammation, neuronal and synpatic loss. This protection is correlated with the hyper-aggregation of Aβ leading to tightly packed, ordered plaques suggesting that one aspect of the protection conferred by reduced IGF signaling is the possible sequestration of soluble Aβ oligomers into dense aggregates of lower toxicity. These findings indicate that the IGF signaling regulated mechanism that protects from Aβ toxicity is conserved from worms to mammals and point to the modulation of this signaling pathway as a promising strategy for the development of Alzheimer's disease therapy.
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DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
2.9
作者：
King, DL;Arendash, GW
通讯作者：
Arendash, GW
影响因子：
4.2
作者：
Blanchard, J.;Martel, G.;Micheau, J.
通讯作者：
Micheau, J.
影响因子：
3.3
作者：
Jensen, MT;Mottin, MD;Arendash, GW
通讯作者：
Arendash, GW
DOI：
10.1073/pnas.0705738104
发表时间：
2007-08-28
影响因子：
11.1
作者：
Fukui, Hirokazu;Diaz, Francisca;Moraes, Carlos T.
通讯作者：
Moraes, Carlos T.