Center for Biomaterials, Biomedical Engineering Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
Center for Biomaterials, Biomedical Engineering Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
Biomaterials. 2021 Dec;279:121232. doi: 10.1016/j.biomaterials.2021.121232. Epub 2021 Oct 28.
Despite growing concerns regarding the threat of airborne nanoparticle-mediated brain degeneration, the underlying pathological mechanisms remain unclear. Carbon nanomaterials, the main components of airborne nanoparticles, have multi-dimensional structures. Therefore, the dimensional effect of carbon-based nanomaterials on the regulation of neural function in brain disorders requires additional clarification. Herein, we report the interaction between zero-to three-dimensional carbon nanostructures and the amyloid-beta protein, which can either activate or interrupt neuronal functions, depending on the dimension of the carbon nanostructures. The carbon nanomaterials induced significant cellular activation by short-term exposure, while prolonged exposure eventually caused neuronal cell death. Such dimension-dependent activation or degeneration was more evident in the higher-dimension carbon nanomaterials, as confirmed by the increases in neurotransmitter secretion and synapse-related protein levels to more than five times at 72 h of monitoring and calcium signaling in the neurons. The inclusion of amyloid-beta proteins ameliorated the cytotoxic effects of carbon nanomaterials in higher-dimensional carbon nanomaterials by regulating 333 genes. We found that the ɑ-synuclein gene is the key factor in carbon-induced abnormal neuronal function. Therefore, through biological analyses and in vitro feasibility studies, this new insight may contribute toward understanding the pathological mechanism and finding a new target for therapy in human brain pathologies.
尽管人们越来越关注空气中纳米颗粒介导的大脑退化的威胁，但潜在的病理机制仍不清楚。碳纳米材料是空气中纳米颗粒的主要成分，具有多维结构。因此，碳基纳米材料对脑疾病中神经功能调节的维度效应需要进一步阐明。在这里，我们报告了零维至三维碳纳米结构与淀粉样蛋白-β之间的相互作用，这取决于碳纳米结构的维度，它可以激活或中断神经元功能。碳纳米材料在短期暴露下会引起明显的细胞激活，而长期暴露最终会导致神经元细胞死亡。这种依赖于维度的激活或退化在更高维度的碳纳米材料中更为明显，这可以通过在监测的 72 小时内神经递质分泌和突触相关蛋白水平增加超过五倍以及神经元中的钙信号来证实。淀粉样蛋白-β 蛋白的加入通过调节 333 个基因减轻了更高维度碳纳米材料中碳纳米材料的细胞毒性作用。我们发现，ɑ-突触核蛋白基因是碳诱导异常神经元功能的关键因素。因此，通过生物学分析和体外可行性研究，这一新的见解可能有助于理解人类大脑病理中的病理机制并找到新的治疗靶点。
