Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits.
Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits.
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DOI：
10.1371/journal.pone.0025416
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Oddo S
中科院分区：
文献类型：
--
作者：
Majumder S;Richardson A;Strong R;Oddo S
先前的研究表明，诱导自噬可以改善与可溶性淀粉样蛋白-β (Aβ)积累相关的早期认知缺陷。然而，诱导自噬对斑块和缠结的影响尚未确定。虽然可溶性Aβ和tau蛋白在阿尔茨海默病（AD）发病机制中代表有毒物质，但有充分的文献证据表明，斑块和缠结也对正常的脑功能有害。因此，在具有斑块和缠结的动物模型中评估诱导自噬的效果是至关重要的。本研究表明，在2个月大的3xTg-AD小鼠的一生中，预防性给予雷帕霉素，可诱导自噬，显著减少斑块、缠结和认知缺陷。相比之下，诱导15个月大的3xTg-AD小鼠自噬，已经形成斑块和缠结，对ad样病理和认知缺陷没有影响。总之，我们表明，在疾病进展早期给予雷帕霉素诱导自噬可能是一种有效的治疗AD的策略。
Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-β (Aβ). However, the effects of inducing autophagy on plaques and tangles are yet to be determined. While soluble Aβ and tau represent toxic species in Alzheimer's disease (AD) pathogenesis, there is well documented evidence that plaques and tangles also are detrimental to normal brain function. Thus, it is critical to assess the effects of inducing autophagy in an animal model with established plaques and tangles. Here we show that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits. In contrast, inducing autophagy in 15-month-old 3xTg-AD mice, which have established plaques and tangles, has no effects on AD-like pathology and cognitive deficits. In conclusion, we show that autophagy induction via rapamycin may represent a valid therapeutic strategy in AD when administered early in the disease progression.
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雷帕霉素在I期试验中针对复发性PTEN缺陷型胶质母细胞瘤患者的抗肿瘤活性。
影响因子：
15.8
作者：
Cloughesy, Tim F.;Yoshimoto, Koji;Nghiemphu, Phioanh;Brown, Kevin;Dang, Julie;Zhu, Shaojun;Hsueh, Teli;Chen, Yinan;Wang, Wei;Youngkin, David;Liau, Linda;Martin, Neil;Becker, Don;Bergsneider, Marvin;Lai, Albert;Green, Richard;Oglesby, Tom;Koleto, Michael;Trent, Jeff;Horvath, Steve;Mischel, Paul S.;Mellinghoff, Ingo K.;Sawyers, Charles L.
通讯作者：
Sawyers, Charles L.
DOI：
10.1073/pnas.1012851108
发表时间：
2010-12-28
影响因子：
11.1
作者：
Caccamo, Antonella;Maldonado, Monica A.;Oddo, Salvatore
通讯作者：
Oddo, Salvatore
影响因子：
2.7
作者：
ENNACEUR, A;DELACOUR, J
通讯作者：
DELACOUR, J
影响因子：
17.1
作者：
Cao, Kan;Graziotto, John J.;Collins, Francis S.
通讯作者：
Collins, Francis S.
影响因子：
4.3
作者：
Cuervo, AM
通讯作者：
Cuervo, AM