Voronezh State University, Voronezh, 394018, Russia.
Voronezh State University of Engineering Technologies, 394036, Voronezh, Russia.
Biochemistry (Mosc). 2022 Sep;87(9):940-956. doi: 10.1134/S0006297922090073.
Methylene blue (MB) is the first fully synthetic compound that had found its way into medicine over 120 years ago as a treatment against malaria. MB has been approved for the treatment of methemoglobinemia, but there are premises for its repurposing as a neuroprotective agent based on the efficacy of this compound demonstrated in the models of Alzheimer's, Parkinson's, and Huntington's diseases, traumatic brain injury, amyotrophic lateral sclerosis, depressive disorders, etc. However, the goal of this review was not so much to focus on the therapeutic effects of MB in the treatment of various neurodegeneration diseases, but to delve into the mechanisms of direct or indirect effect of this drug on the signaling pathways. MB can act as an alternative electron carrier in the mitochondrial respiratory chain in the case of dysfunctional electron transport chain. It also displays the anti-inflammatory and anti-apoptotic effects, inhibits monoamine oxidase (MAO) and nitric oxide synthase (NOS), activates signaling pathways involved in the mitochondrial pool renewal (mitochondrial biogenesis and autophagy), and prevents aggregation of misfolded proteins. Comprehensive understanding of all aspects of direct and indirect influence of MB, and not just some of its effects, can help in further research of this compound, including its clinical applications.
亚甲蓝（MB）是 120 多年前第一种完全合成的化合物，作为治疗疟疾的药物进入医学领域。MB 已被批准用于治疗高铁血红蛋白血症，但基于该化合物在阿尔茨海默病、帕金森病和亨廷顿病、创伤性脑损伤、肌萎缩侧索硬化症、抑郁障碍等模型中显示出的疗效，有理由将其重新用于神经保护剂。然而，本综述的目的与其说是关注 MB 在治疗各种神经退行性疾病中的治疗效果，不如说是深入研究该药物对信号通路的直接或间接作用机制。在电子传递链功能障碍的情况下，MB 可以作为线粒体呼吸链中的替代电子载体。它还具有抗炎和抗细胞凋亡作用，抑制单胺氧化酶（MAO）和一氧化氮合酶（NOS），激活涉及线粒体池更新（线粒体生物发生和自噬）的信号通路，并防止错误折叠蛋白质的聚集。全面了解 MB 的直接和间接影响的所有方面，而不仅仅是其某些作用，可以帮助进一步研究该化合物，包括其临床应用。
