Aydin Nursah, Turkez Hasan, Tozlu Ozlem Ozdemir, Arslan Mehmet Enes, Yavuz Mehmet, Sonmez Erdal, Ozpolat Ozgur Fırat, Cacciatore Ivana, Di Stefano Antonio, Mardinoglu Adil
Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum 25050, Turkey.
Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey.
Nanomaterials (Basel). 2022 Aug 5;12(15):2690. doi: 10.3390/nano12152690.
Alzheimer’s disease (AD) is considered as the most common neurodegenerative disease. Extracellular amyloid beta (Aβ) deposition is a hallmark of AD. The options based on degradation and clearance of Aβ are preferred as promising therapeutic strategies for AD. Interestingly, recent findings indicate that boron nanoparticles not only act as a carrier but also play key roles in mediating biological effects. In the present study, the aim was to investigate the effects of different concentrations (0−500 mg/L) of hexagonal boron nitride nanoparticles (hBN-NPs) against neurotoxicity by beta amyloid (Aβ1-42) in differentiated human SH-SY5Y neuroblastoma cell cultures for the first time. The synthesized hBN-NPs were characterized by X-ray diffraction (XRD) measurements, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Aβ1-42-induced neurotoxicity and therapeutic potential by hBN-NPs were assessed on differentiated SH-SY5Y cells using MTT and LDH release assays. Levels of total antioxidant capacity (TAC) and total oxidant status (TOS), expression levels of genes associated with AD and cellular morphologies were examined. The exposure to Aβ1-42 significantly decreased the rates of viable cells which was accompanied by elevated TOS level. Aβ1-42 induced both apoptotic and necrotic cell death. Aβ exposure led to significant increases in expression levels of APOE, BACE 1, EGFR, NCTSN and TNF-α genes and significant decreases in expression levels of ADAM 10, APH1A, BDNF, PSEN1 and PSENEN genes (p < 0.05). All the Aβ1-42-induced neurotoxic insults were inhibited by the applications with hBN-NPs. hBN-NPs also suppressed the remarkable elevation in the signal for Aβ following exposure to Aβ1-42 for 48 h. Our results indicated that hBN-NPs could significantly prevent the neurotoxic damages by Aβ. Thus, hBN-NPs could be a novel and promising anti-AD agent for effective drug development, bio-nano imaging or drug delivery strategies.
阿尔茨海默病（AD）被认为是最常见的神经退行性疾病。细胞外β淀粉样蛋白（Aβ）沉积是AD的一个标志。基于Aβ降解和清除的方法作为AD有前景的治疗策略更受青睐。有趣的是，最近的研究结果表明硼纳米颗粒不仅作为载体，而且在介导生物学效应中发挥关键作用。在本研究中，目的是首次研究不同浓度（0−500 mg/L）的六方氮化硼纳米颗粒（hBN-NPs）对分化的人SH-SY5Y神经母细胞瘤细胞培养物中β淀粉样蛋白（Aβ1-42）诱导的神经毒性的影响。通过X射线衍射（XRD）测量、扫描电子显微镜（SEM）和透射电子显微镜（TEM）对合成的hBN-NPs进行表征。使用MTT和LDH释放试验评估hBN-NPs对分化的SH-SY5Y细胞的Aβ1-42诱导的神经毒性和治疗潜力。检测总抗氧化能力（TAC）和总氧化状态（TOS）水平、与AD相关的基因表达水平以及细胞形态。暴露于Aβ1-42显著降低了活细胞率，同时TOS水平升高。Aβ1-42诱导凋亡和坏死性细胞死亡。Aβ暴露导致载脂蛋白E（APOE）、β-分泌酶1（BACE 1）、表皮生长因子受体（EGFR）、神经钙黏蛋白（NCTSN）和肿瘤坏死因子-α（TNF-α）基因表达水平显著升高，而ADAM金属蛋白酶10（ADAM 10）、早老素增强子1（APH1A）、脑源性神经营养因子（BDNF）、早老素1（PSEN1）和早老素增强子（PSENEN）基因表达水平显著降低（p < 0.05）。hBN-NPs的应用抑制了所有Aβ1-42诱导的神经毒性损伤。hBN-NPs还抑制了暴露于Aβ1-42 48小时后Aβ信号的显著升高。我们的结果表明，hBN-NPs可以显著预防Aβ诱导的神经毒性损伤。因此，hBN-NPs可能是一种新型且有前景的抗AD药物，可用于有效的药物开发、生物纳米成像或药物递送策略。
