Clemastine attenuates AD-like pathology in an AD model mouse via enhancing mTOR-mediated autophagy
Clemastine attenuates AD-like pathology in an AD model mouse via enhancing mTOR-mediated autophagy
复制标题
氯马斯汀通过增强 mTOR 介导的自噬来减轻 AD 模型小鼠的 AD 样病理学
DOI：
10.1016/j.expneurol.2021.113742
复制
发表时间：
2021-05-15
影响因子：
5.3
通讯作者：
Ma, Quan-Hong
中科院分区：
文献类型：
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作者：
Li, Zhen-Yu;Chen, Li-Hua;Ma, Quan-Hong
阿尔茨海默病(AD)是一种神经退行性疾病，治疗药物有限。增强自噬可减轻各种AD模型小鼠的AD病理。因此，开发潜在的促进自噬的药物可能会给AD的治疗带来有益的效果。在本研究中，我们展示了氯马汀，一种第一代组胺H1R拮抗剂，最初用于治疗变应性鼻炎，改善APP/PS1转基因小鼠的AD发病机制。长期口服氯马斯汀可减少APP/PS1转基因小鼠的淀粉样β蛋白(Aβ)负荷、神经炎症和认知缺陷。氯马斯汀通过降低APP的BACE1、CTF水平减少Aβ生成。从机制上讲，氯马斯汀在增强自噬的同时抑制mTOR信号。因此，我们认为氯马斯汀通过增强mTOR介导的自噬来减轻AD的病理。
Alzheimer's disease (AD) is a neurodegenerative disorder with limited available drugs for treatment. Enhancing autophagy attenuates AD pathology in various AD model mice. Thus, development of potential drugs which enhance autophagy may bring beneficial effects in AD therapy. In the present study, we show clemastine, a firstgeneration histamine H1R antagonist and being originally marketed for the treatment of allergic rhinitis, ameliorates AD pathogenesis in APP/PS1 transgenic mice. Chronic treatment with clemastine orally reduced amyloid-beta (A beta) load, neuroinflammation and cognitive deficits of APP/PS1 transgenic mice. Clemastine decreases A beta generation via reducing the levels of BACE1, CTFs of APP. Mechanistically, clemastine enhances autophagy concomitant with a suppression of mTOR signaling. Therefore, we propose that clemastine attenuates AD pathology via enhancing mTOR-mediated autophagy.