Alzheimer's disease (AD) is one of the most common age-associated brain diseases and is induced by the accumulation of amyloid beta (Aβ) and oxidative stress. Many studies have focused on eliminating Aβ by nanoparticle affinity; however, nanoparticles are taken up mainly by microglia rather than neurons, leading poor control of AD. Herein, mitochondria-targeted nanozymes known as (3-carboxypropyl)triphenyl-phosphonium bromide-conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000]-functionalized molybdenum disulfide quantum dots (TPP-MoS2 QDs) were designed. TPP-MoS2 QDs mitigate Aβ aggregate-mediated neurotoxicity and eliminate Aβ aggregates in AD mice by switching microglia from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype. TPP-MoS2 QDs cross the blood-brain barrier, escape from lysosomes, target mitochondria and exhibit the comprehensive activity of a bifunctional nanozyme, thus preventing spontaneous neuroinflammation by regulating the proinflammatory substances interleukin-1β, interleukin-6 and tumor necrosis factors as well as the anti-inflammatory substance transforming growth factor-β. In contrast to the low efficacy of eliminating Aβ by nanoparticle affinity, the present study provides a new pathway to mitigate AD pathology through mitochondria-targeted nanozymes and M1/M2 microglial polarization.

中文翻译：

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具有双重酶活性的针对线粒体的TPP-MoS2通过Alzheimer病模型中的M1 / M2小胶质细胞极化提供有效的神经保护。

阿尔茨海默氏病（AD）是最常见的与年龄相关的脑部疾病之一，由淀粉样β（Aβ）积累和氧化应激诱发。许多研究集中在通过纳米粒子亲和力消除Aβ上。然而，纳米颗粒主要被小胶质细胞而不是神经元吸收，导致对AD的不良控制。在此，称为（3-羧丙基）三苯基-溴化-的1,2-二硬脂酰基-sn-甘油-3-磷酸乙醇胺-N- [氨基（聚乙二醇）-2000]-官能化的二硫化钼量子点的线粒体靶向纳米酶（TPP-MoS2 QDs）被设计。TPP-MoS2 QD通过将小胶质细胞从促炎M1表型切换为消炎M2表型，减轻了Aβ聚集体介导的神经毒性，并消除了AD小鼠中的Aβ聚集体。TPP-MoS2量子点穿过血脑屏障，从溶酶体中逃脱出来，靶向线粒体并显示出双功能纳米酶的全面活性，从而通过调节促炎物质白介素-1β，白介素-6和肿瘤坏死因子以及抗炎物质转化生长因子-β来防止自发性神经炎症。与通过纳米粒子亲和力消除Aβ的低功效相反，本研究提供了一条新途径，可通过线粒体靶向的纳米酶和M1 / M2小胶质细胞极化来减轻AD病理。白细胞介素6和肿瘤坏死因子以及抗炎物质转化生长因子β。与通过纳米粒子亲和力消除Aβ的低功效相反，本研究提供了一条新途径，可通过线粒体靶向的纳米酶和M1 / M2小胶质细胞极化来减轻AD病理。白细胞介素6和肿瘤坏死因子以及抗炎物质转化生长因子-β。与通过纳米粒子亲和力消除Aβ的低功效相反，本研究提供了一条新途径，可通过线粒体靶向的纳米酶和M1 / M2小胶质细胞极化来减轻AD病理。