摘要
阿尔茨海默病(AD)是中枢神经系统中最常见的神经退行性疾病。目前用于AD的治疗手段只能缓解其症状,针对该疾病的病理过程的治疗策略仍然是难以捉摸的。氟西汀( FLX )是最广泛使用的用于与AD相关的抑郁症和焦虑症治疗的抗抑郁药,然而,是否该药物会影响该疾病的发病机制是未知的。我们发现,FLX能改善APP / PS1小鼠,一个很好的典型AD模型的空间记忆,学习能力和情感行为。在相同小鼠上,FLX有效地防止突触素(SYP)和微管相关蛋白2( MAP2 )的蛋白质损失。FLX无法防止斑块形成,但显著降低脑组织、脑脊髓液(CSF)和血清中高浓度的可溶性β -淀粉样蛋白(Aβ)。FLX还能有效地抑制淀粉样前体蛋白(APP)在T668 的磷酸化,可能是APP / PS1小鼠治疗后Aβ生成减少的一个机制。
关键词: 淀粉样前体蛋白(APP),阿尔茨海默病(AD),行为,氟西汀,可溶性Aβ
Current Alzheimer Research
Title:Fluoxetine Improves Behavioral Performance by Suppressing the Production of Soluble β-Amyloid in APP/PS1 Mice
Volume: 11 Issue: 7
Author(s): Junhui Wang, Yanbo Zhang, Haiyun Xu, Shenghua Zhu, Hongxing Wang, Jue He, Handi Zhang, Huining Guo, Jiming Kong, Qingjun Huang and Xin-Min Li
Affiliation:
关键词: 淀粉样前体蛋白(APP),阿尔茨海默病(AD),行为,氟西汀,可溶性Aβ
摘要: Alzheimer’s disease (AD) is the most common neurodegenerative disorder of the central nervous system. Current approaches for AD treatment only ameliorate symptoms. Therapeutic strategies that target the pathological processes of the disease remain elusive. Fluoxetine (FLX) is one of the most widely used antidepressants for the treatment of depression and anxiety associated with AD, however, it is unknown if the drug affects the pathogenesis of the disease. We showed that FLX improved spatial memory, learning and emotional behaviors of APP/PS1 mice, a well characterized model of AD. In the same mice, FLX effectively prevented the protein loss of synaptophysin (SYP) and microtubuleassociated protein 2 (MAP2). FLX was unable to prevent plaque formation, but significantly lowered high levels of soluble β-amyloid (Aβ) in brain tissue, cerebrospinal fluid (CSF) and blood sera. FLX also effectively inhibited the phosphorylation of amyloid precursor protein (APP) at T668, which may be a possible mechanism of the reduced Aβ production in APP/PS1 mouse after treatment.
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Wang Junhui, Zhang Yanbo, Xu Haiyun, Zhu Shenghua, Wang Hongxing, He Jue, Zhang Handi, Guo Huining, Kong Jiming, Huang Qingjun and Li Xin-Min, Fluoxetine Improves Behavioral Performance by Suppressing the Production of Soluble β-Amyloid in APP/PS1 Mice, Current Alzheimer Research 2014; 11 (7) . https://dx.doi.org/10.2174/1567205011666140812114715
DOI https://dx.doi.org/10.2174/1567205011666140812114715 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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