The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer's disease.
The novel estrogen receptor modulator STX attenuates Amyloid-β neurotoxicity in the 5XFAD mouse model of Alzheimer's disease.
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DOI：
10.1016/j.nbd.2022.105888
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发表时间：
2022-11
影响因子：
6.1
通讯作者：
Copenhaver, Philip F.
中科院分区：
文献类型：
--
作者：
Quinn, Joseph F.;Kelly, Martin J.;Harris, Christopher J.;Hack, Wyatt;Gray, Nora E.;Kulik, Veronika;Bostick, Zoe;Brumbach, Barbara H.;Copenhaver, Philip F.
基于非甾体雌激素受体调节剂STX在体外减轻神经毒性β淀粉样蛋白（Aβ）的作用的先前证据，我们评估了其在阿尔茨海默病小鼠模型中的神经保护益处。在两个月大时开始积累脑Aβ的5XFAD小鼠的队列在6个月大时开始用口服施用的STX治疗两个月。行为测试后，以评估认知功能，生化和免疫组化分析用于分析线粒体功能和突触完整性的关键标志物。如先前在培养的神经元中所记录的，口服STX治疗减弱了脑中Aβ相关的线粒体毒性和突触毒性。STX还适度改善了5XFAD小鼠的空间记忆。此外，STX减少了淀粉样斑块周围的反应性星形细胞增多和小胶质细胞增生的标志物，并且还意外地降低了大脑中大脑Aβ的总体水平。STX的神经保护作用在女性中比在男性中更强。这些结果表明，STX可能具有治疗阿尔茨海默病的潜力。
Based on previous evidence that the non-steroidal estrogen receptor modulator STX mitigates the effects of neurotoxic Amyloid-β (Aβ) in vitro, we have evaluated its neuroprotective benefits in a mouse model of Alzheimer’s disease. Cohorts of 5XFAD mice, which begin to accumulate cerebral Aβ at two months of age, were treated with orally-administered STX starting at 6 months of age for two months. After behavioral testing to evaluate cognitive function, biochemical and immunohistochemical assays were used to analyze key markers of mitochondrial function and synaptic integrity. Oral STX treatment attenuated Aβ-associated mitochondrial toxicity and synaptic toxicity in the brain, as previously documented in cultured neurons. STX also moderately improved spatial memory in 5XFAD mice. In addition, STX reduced markers for reactive astrocytosis and microgliosis surrounding amyloid plaques, and also unexpectedly reduced overall levels of cerebral Aβ in the brain. The neuroprotective effects of STX were more robust in females than in males. These results suggest that STX may have therapeutic potential in Alzheimer’s Disease.
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口服锌减轻了TG2576小鼠的淀粉样蛋白负担。
DOI：
10.3233/jad-131703
发表时间：
2014
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
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作者：
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发表时间：
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期刊：
Molecular and cellular neurosciences
影响因子：
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作者：
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影响因子：
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作者：
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Ahmed SB
影响因子：
2.7
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