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Proton Stimulation Targeting Plaque Magnetite Reduces Amyloid-β Plaque and Iron Redox Toxicity and Improves Memory in an Alzheimer’s Disease Mouse Model
Journal of Alzheimer’s Disease ( IF 4 ) Pub Date : 2021-09-18 , DOI: 10.3233/jad-210739
Seung-Jun Seo 1 , Won-Seok Chang 1 , Jae-Geun Jeon 1 , Younshick Choi 1 , EunHo Kim 2 , Jong-Ki Kim 1
Affiliation  

Background:The coexistence of magnetite within protein aggregates in the brain is a typical pathologic feature of Alzheimer’s disease (AD), and the formation of amyloid-β (Aβ) plaques induces critical impairment of cognitive function. Objective:This study aimed to investigate the therapeutic effectof proton stimulation (PS) targeting plaque magnetite in the transgenic AD mouse brain. Methods:A proton transmission beam was applied to the whole mouse brain at a single entrance dose of 2 or 4 Gy to test the effect of disruption of magnetite-containing Aβ plaques by electron emission from magnetite. The reduction in Aβ plaque burden and the cognitive function of the PS-treated mouse group were assayed by histochemical analysis and memory tests, respectively. Aβ-magnetite and Aβ fibrils were treated with PS to investigate the breakdown of the amyloid protein matrix. Results:Single PS induced a 48–87%reduction in both the amyloid plaque burden and ferrous-containing magnetite level in the early-onset AD mouse brain while saving normal tissue. The overall Aβ plaque burden (68–82%) and (94–97%) hippocampal magnetite levels were reduced in late onset AD mice that showed improvements in cognitive function after PS compared with untreated AD mice (p < 0.001). Analysis of amyloid fibrils after exposure to a single 2 or 4 Gy proton transmission beam demonstrated that the protein matrix was broken down only in magnetite-associated Aβ fibrils. Conclusion:Single PS targeting plaque magnetite effectively decreases the amyloid plaque burden and the ferrous-containing magnetite level, and this effect is useful for memory recovery.

中文翻译:

靶向斑块磁铁矿的质子刺激可降低淀粉样蛋白 β 斑块和铁氧化还原毒性并改善阿尔茨海默病小鼠模型的记忆力

背景:大脑中蛋白质聚集体中磁铁​​矿的共存是阿尔茨海默病 (AD) 的典型病理特征,淀粉样蛋白 β (Aβ) 斑块的形成会导致认知功能的严重损害。目的:本研究旨在探讨质子刺激(PS)靶向斑块磁铁矿在转基因 AD 小鼠脑中的治疗效果。方法:以 2 或 4 Gy 的单次入口剂量将质子传输束应用于整个小鼠大脑,以测试磁铁矿电子发射对含磁铁矿 Aβ 斑块的破坏效果。分别通过组织化学分析和记忆测试来测定 Aβ 斑块负荷的减少和 PS 处理的小鼠组的认知功能。用 PS 处理 Aβ-磁铁矿和 Aβ 原纤维以研究淀粉样蛋白基质的分解。结果:单一 PS 诱导早发性 AD 小鼠大脑中淀粉样蛋白斑块负荷和含铁磁铁矿水平降低 48-87%,同时保存正常组织。与未治疗的 AD 小鼠相比,PS 后认知功能有所改善的晚发性 AD 小鼠的总体 Aβ 斑块负荷(68-82%)和(94-97%)海马磁铁矿水平降低(p < 0.001)。暴露于单个 2 或 4 Gy 质子传输束后对淀粉样原纤维的分析表明,蛋白质基质仅在与磁铁矿相关的 Aβ 原纤维中分解。结论:单一PS靶向斑块磁铁矿有效降低淀粉样斑块负荷和含铁磁铁矿水平,
更新日期:2021-09-22
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