PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is a neurodegenerative disease that badly impacts patients and their caregivers. AD is characterized by deposition of amyloid beta (Aβ) and phosphorylated tau protein (pTau) in the brain with underlying neuroinflammation. We aimed to develop a neuroprotective paradigm by loading verapamil (VRH) into hyaluronic acid-modified carbon quantum dots (CQDs) and comparing its effectiveness with the free form in an AD-like model in rats induced by lipopolysaccharide (LPS). The experimental rats were divided into seven groups: control, LPS, CQDs, early free VRH (FVRH), late FVRH, early verapamil carbon quantum dots (VCQDs), and late VCQDs. Characterizations of VCQDs, the behavioral performance of the rats, histopathological and immunohistochemical changes, some AD hallmarks, oxidative stress biomarkers, neuro-affecting genes, and DNA fragmentation were determined. VRH was successfully loaded into CQDs, which was confirmed by the measured parameters. VRH showed enhancement in cognitive functions, disruption to the architecture of the brain, decreased Aβ and pTau, increased antioxidant capacity, modifiable expression of genes, and a decline in DNA fragmentation. The loaded therapy was superior to the free drug. Moreover, the early intervention was better than the late, confirming the implication of the detected molecular targets in the development of AD. VRH showed multifaceted mechanisms in combating LPS-induced neurotoxicity through its anti-inflammatory and antioxidant properties, thereby mitigating the hallmarks of AD. Additionally, the synthesized nanosystem approach exhibited superior neuroprotection owing to the advantages offered by CQDs. However, finding new actionable biomarkers and molecular targets is of decisive importance to improve the outcomes for patients with AD.
摘要：
阿尔茨海默病（AD）是一种严重影响患者及其护理人员的神经退行性疾病。AD的特征在于脑中淀粉样蛋白β(Aβ)和磷酸化tau蛋白(pTau)的沉积以及潜在的神经炎症。我们旨在通过将维拉帕米（VRH）加载到透明质酸修饰的碳量子点（CQDs）中，并将其有效性与脂多糖（LPS）诱导的大鼠AD样模型中的游离形式进行比较来开发神经保护范例。实验大鼠分为7组:对照组,LPS,CQDs,早期免费VRH（FVRH），晚期FVRH,早期维拉帕米碳量子点（VCQDs），和后期的VCQDs。VCQDs的表征，大鼠的行为表现，组织病理学和免疫组织化学改变，一些AD标志，氧化应激生物标志物，影响神经的基因，并确定DNA片段化。VRH已成功加载到CQD中,这得到了测量参数的证实。VRH显示认知功能增强，大脑结构的破坏，Aβ和pTau降低，增加抗氧化能力，基因的可修改表达，和DNA片段的减少。负载疗法优于游离药物。此外，早期干预比晚期干预好，证实检测到的分子靶标在AD发展中的意义。VRH通过其抗炎和抗氧化特性在对抗LPS诱导的神经毒性方面表现出多方面的机制。从而减轻AD的标志。此外,由于CQDs提供的优势，合成的纳米系统方法表现出优异的神经保护作用。然而,发现新的可操作的生物标志物和分子靶标对于改善AD患者的预后具有决定性的重要性.
