Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan.
Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan.
ACS Chem Neurosci. 2023 Aug 16;14(16):2922-2934. doi: 10.1021/acschemneuro.3c00348. Epub 2023 Aug 2.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment, memory loss, and behavioral deficits. β-amyloid (Aβ) aggregation is a significant cause of the pathogenesis in AD. Despite the numerous types of research, the current treatment efficacy remains insufficient. Hence, a novel therapeutic strategy is required. Nitric oxide (NO) is a multifunctional gaseous molecule. NO displays a neuroprotective role in the central nervous system by inhibiting the Aβ aggregation and rescuing memory and learning deficit through the NO signaling pathway. Targeting the NO pathway might be a therapeutic option; however, NO has a limited half-life under the biological system. To address this issue, a biomimetic dinitrosyl iron complex [(NO)Fe(μ-SCHCHCOOH)Fe(NO)] () that could stably deliver NO was explored in the current study. To determine whether exerts anti-AD efficacy, was added to neuron-like cells and primary cortical neurons along with Aβ. This study found that protected neuronal cells from Aβ-induced cytotoxicity, potentiated neuronal functions, and facilitated Aβ degradation through the NO-sGC-cGMP-AKT-GSK3β-CREB/MMP-9 pathway.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是认知障碍、记忆力减退和行为缺陷。β-淀粉样蛋白（Aβ）聚集是 AD 发病机制的重要原因。尽管有多种类型的研究，但目前的治疗效果仍然不足。因此，需要一种新的治疗策略。一氧化氮（NO）是一种多功能气态分子。NO 通过抑制 Aβ聚集，通过 NO 信号通路挽救记忆和学习缺陷，在中枢神经系统中发挥神经保护作用。靶向 NO 通路可能是一种治疗选择；然而，NO 在生物系统中的半衰期有限。为了解决这个问题，本研究探索了一种仿生双硝酰基铁配合物 [(NO)Fe(μ-SCHCHCOOH)Fe(NO)] ()，它可以稳定地输送 NO。为了确定 是否具有抗 AD 功效，将 与 Aβ一起添加到神经元样细胞和原代皮质神经元中。这项研究发现， 可以保护神经元细胞免受 Aβ诱导的细胞毒性，增强神经元功能，并通过 NO-sGC-cGMP-AKT-GSK3β-CREB/MMP-9 通路促进 Aβ降解。
