Fluoxetine protects against amyloid-beta toxicity, in part via daf-16 mediated cell signaling pathway, in Caenorhabditis elegans.
Fluoxetine protects against amyloid-beta toxicity, in part via daf-16 mediated cell signaling pathway, in Caenorhabditis elegans.
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氟西汀可部分通过 daf-16 介导的细胞信号传导途径保护秀丽隐杆线虫免受 β 淀粉样蛋白毒性。
DOI：
10.1016/j.neuropharm.2010.04.008
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发表时间：
2010-09
影响因子：
4.7
通讯作者：
Luo, Yuan
中科院分区：
文献类型：
--
作者：
Keowkase, Roongpetch;Aboukhatwa, Marwa;Luo, Yuan
阿尔茨海默病（AD）是一种进行性神经退行性疾病，是老年人中最常见的痴呆症。β淀粉样蛋白（Aβ）的积累是阿尔茨海默病的组织病理学标志之一。Aβ聚集形成寡聚物，对神经元有毒，对阿尔茨海默病的发生和发展至关重要。在秀丽隐杆线虫（C. elegans） AD模型中，人a β在体壁肌肉的细胞内表达。Aβ在肌肉中的表达和随后的聚集导致进行性瘫痪。虽然作用机制尚不清楚，但抗抑郁药已与FDA批准的治疗阿尔茨海默氏症痴呆的药物一起使用，并已在阿尔茨海默氏症的人类和动物模型中显示出增强认知功能的作用。我们发现抗抑郁药氟西汀，一种选择性5 -羟色胺再摄取抑制剂，通过减少a β低聚物，显著延缓了a β诱导的秀丽隐杆线虫a β毒性模型的瘫痪。我们的研究结果表明，胰岛素信号和DAF-16/FOXO转录因子在氟西汀介导的延迟性麻痹中是必需的。我们还发现氟西汀增加了耐热性，延长了寿命。这一发现表明氟西汀可能通过降低蛋白质毒性对阿尔茨海默病的治疗有益。
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and is the most common form of dementia in elderly people. The accumulation of amyloid β (Aβ) is one of the histopathological hallmarks of AD. Aβ is aggregated to form oligomers which are toxic to neurons and are critical to the onset and progression of AD. In a Caenorhabditis elegans (C. elegans) model of AD, human Aβ is expressed intracellularly in the body wall muscle. The expression and subsequent aggregation of Aβ in the muscle lead to progressive paralysis. Although the mechanism of action is unknown, antidepressants have been used with FDA approved drugs for dementia in AD and have been shown to enhance cognitive function in human and in animal models of AD. We found that the antidepressant fluoxetine, a selective serotonin reuptake inhibitor, significantly delayed Aβ-induced paralysis in the C. elegans model of Aβ toxicity by reducing Aβ oligomers. Our result showed that insulin signaling and DAF-16/FOXO transcription factor were required for fluoxetine-mediated delayed paralysis. We also found that fluoxetine increased thermal stress resistance and extended life span. This finding suggests that fluoxetine may have benefit for the treatment of AD by reduction of proteotoxicity.
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DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
DOI：
10.1016/s0163-1047(87)90574-7
发表时间：
1987-07-01
期刊：
BEHAVIORAL AND NEURAL BIOLOGY
影响因子：
--
作者：
ALTMAN, HJ;STONE, WS;OGREN, SO
通讯作者：
OGREN, SO
影响因子：
3.3
作者：
Dempsey, CM;Mackenzie, SM;Sze, JY
通讯作者：
Sze, JY
影响因子：
4
作者：
Finkel, SI;Mintzer, JE;McRae, T
通讯作者：
McRae, T
影响因子：
4.7
作者：
Lakso, M;Vartiainen, S;Wong, G
通讯作者：
Wong, G