The degeneration of neurons due to the accumulation of misfolded amyloid aggregates in the central nervous system (CNS) is a fundamental neuropathology of Alzheimer's disease (AD). It is believed that dislodging/clearing these amyloid aggregates from the neuronal tissues could lead to a potential cure for AD. In the present work, we explored biocompatible polydopamine-coated piezoelectric polyvinylidene fluoride (DPVDF) nanospheres as acoustic stimulus-triggered anti-fibrillating and anti-amyloid agents. The nanospheres were tested against two model amyloidogenic peptides, including the reductionist model-based amyloidogenic dipeptide, diphenylalanine, and the amyloid polypeptide, amyloid beta (Aβ42). Our results revealed that DPVDF nanospheres could effectively disassemble the model peptide-derived amyloid fibrils under suitable acoustic stimulation. In vitro studies also showed that the stimulus activated DPVDF nanospheres could efficiently alleviate the neurotoxicity of FF fibrils as exemplified in neuroblastoma, SHSY5Y, cells. Studies carried out in animal models further validated that the nanospheres could dislodge amyloid aggregates in vivo and also help the animals regain their cognitive behavior. Thus, these acoustic stimuli-activated nanospheres could serve as a novel class of disease-modifying nanomaterials for non-invasive electro-chemotherapy of Alzheimer's disease.

中文翻译：

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未来的阿尔茨海默病疗法：声刺激压电纳米球可减少淀粉样蛋白

由于中枢神经系统（CNS）中错误折叠的淀粉样蛋白聚集物的积累而导致的神经元退化是阿尔茨海默病（AD）的基本神经病理学。据信，从神经元组织中去除/清除这些淀粉样蛋白聚集物可能会导致 AD 的潜在治愈。在目前的工作中，我们探索了生物相容性聚多巴胺涂层压电聚偏二氟乙烯（DPVDF）纳米球作为声刺激触发的抗纤维性颤动和抗淀粉样蛋白药物。纳米球针对两种模型淀粉样蛋白肽进行了测试，包括基于还原模型的淀粉样蛋白生成二肽、二苯丙氨酸和淀粉样蛋白多肽、淀粉样蛋白β (Aβ42)。我们的结果表明，DPVDF 纳米球在适当的声刺激下可以有效地分解模型肽衍生的淀粉样原纤维。体外研究还表明，刺激激活的 DPVDF 纳米球可以有效减轻 FF 原纤维的神经毒性，如神经母细胞瘤 SHSY5Y 细胞中的例子。在动物模型中进行的研究进一步证实，纳米球可以去除体内淀粉样蛋白聚集物，并帮助动物恢复认知行为。因此，这些声刺激激活的纳米球可以作为一类新型的疾病缓解纳米材料，用于阿尔茨海默病的非侵入性电化学疗法。