Biochemistry Department, Faculty of Pharmacy, Menoufia University, Shebin El-Kom 32511, Menoufia, Egypt.
Genetic Engineering and Molecular Biology Division, Department of Zoology, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Menoufia, Egypt.
Int J Mol Sci. 2024 Jul 16;25(14):7790. doi: 10.3390/ijms25147790.
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.
阿尔茨海默病（AD）是一种神经退行性疾病，严重影响患者及其护理人员。AD 的特征是大脑中淀粉样β（Aβ）和磷酸化 tau 蛋白（pTau）的沉积，伴有潜在的神经炎症。我们旨在通过将维拉帕米（VRH）载入透明质酸修饰的碳量子点（CQDs）中来开发一种神经保护范式，并在 LPS 诱导的 AD 样大鼠模型中比较其与游离形式的有效性。实验大鼠分为七组：对照组、LPS 组、CQDs 组、早期游离 VRH（FVRH）组、晚期 FVRH 组、早期维拉帕米碳量子点（VCQDs）组和晚期 VCQDs 组。对 VCQDs 的特性、大鼠的行为表现、组织病理学和免疫组织化学变化、一些 AD 标志物、氧化应激生物标志物、神经影响基因和 DNA 片段化进行了测定。通过测量参数证实 VRH 成功载入 CQDs。VRH 显示认知功能增强，破坏大脑结构，减少 Aβ和 pTau，增加抗氧化能力，基因表达可调节，DNA 片段化减少。负载治疗优于游离药物。此外，早期干预优于晚期干预，这证实了所检测的分子靶标在 AD 发展中的意义。VRH 通过其抗炎和抗氧化特性显示出对抗 LPS 诱导的神经毒性的多方面机制，从而减轻 AD 的特征。此外，由于 CQDs 提供的优势，合成的纳米系统方法表现出优越的神经保护作用。然而，寻找新的可操作的生物标志物和分子靶标对于改善 AD 患者的预后至关重要。
