阿尔茨海默病 (AD) 是最常见的神经退行性疾病，病理上由淀粉样蛋白 - β 蛋白 (Aβ) 聚集、氧化应激和神经炎症引起。 AD 的发病机制仍不清楚且错综复杂，有效的治疗方法也很少有记录。因此，发现淀粉样蛋白调节剂被认为是预防和治疗 AD 的一个有前途的途径。在这项研究中，人血清白蛋白（HSA），一种基于蛋白质的Aβ抑制剂，被用作模板，通过生物矿化指导HSA-二氧化锰纳米复合材料（HMn NCs）的合成。 HSA中原位形成的MnO2赋予该纳米平台出色的活性氧（ROS）清除能力，包括超氧化物歧化酶模拟和过氧化氢酶模拟活性，可以清除过多的超氧阴离子自由基和过氧化氢。更重要的是，与 HSA 相比，HMn NCs 在抑制 Aβ 纤维化方面表现出增强的效力，这通过清除过量的 ROS 进一步减轻了 Aβ 介导的 SH-SY5Y 神经毒性。此外，研究表明，HMn NCs 通过降低肿瘤坏死因子-α 和白细胞介素-6 来减少 BV-2 细胞中 Aβ 相关的炎症。此外，转基因线虫研究表明，HMn NCs可以去除Aβ斑块，减少CL2006线虫体内的ROS，并促进线虫寿命的延长。因此，HMn NCs 提供了一种有前途的策略，以促进多功能纳米复合材料在 AD 治疗中的应用。

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease pathologically caused by amyloid-β protein (Aβ) aggregation, oxidative stress, and neuroinflammation. The pathogenesis of AD is still uncertain and intricate, and helpful therapy has rarely been recorded. So, discovering amyloid modulators is deemed a promising avenue for preventing and treating AD. In this study, human serum albumin (HSA), a protein-based Aβ inhibitor, was utilized as a template to guide the synthesis of HSA-manganese dioxide nanocomposites (HMn NCs) through biomineralization. The in situ formed MnO2 in HSA endows this nano-platform with outstanding reactive oxygen species (ROS) scavenging capability, including superoxide dismutase-mimetic and catalase-mimetic activities, which could scavenge the plethora of superoxide anion radicals and hydrogen peroxide. More importantly, the HMn NCs show enhanced potency in suppressing Aβ fibrillization compared with HSA, which further alleviates Aβ-mediated SH-SY5Y neurotoxicity by scavenging excessive ROS. Moreover, it is demonstrated that HMn NCs reduce Aβ-related inflammation in BV-2 cells by lowering tumor necrosis factor-α and interleukin-6. Furthermore, transgenic C. elegans studies showed that HMn NCs could remove Aβ plaques, reduce ROS in CL2006 worms, and promote the lifespan extension of worms. Thus, HMn NCs provide a promising tactic to facilitate the application of multifunctional nanocomposites in AD treatment.