Frecska Ede, Kovács Attila, Szabo Attila
Department of Psychiatry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Psychiatry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Int Rev Neurobiol. 2025;181:395-420. doi: 10.1016/bs.irn.2025.04.010. Epub 2025 Jun 11.
This paper explores the therapeutic potential of DMT in neuroprotective strategies, particularly concerning ischemia-reperfusion injury (IRI) and neurodegenerative disorders. Besides its potent serotonin receptor actions, DMT is also an endogenous agonist of the sigma-1 receptor (Sig-1R). Sigma receptors are a unique family of proteins with high expression in the brain and spinal cord and have been involved in the etiology, symptom course and treatment of several central nervous system disorders. Our previous theoretical and experimental work strongly suggest that targeting sigma (and serotonin) receptors via DMT may be particularly useful for treatment in a number of neurological conditions like stroke, global brain ischemia, Alzheimer's disease, and amyotrophic lateral sclerosis. In this article, we briefly overview the function of Sig1-R in cellular bioenergetics with a focus on the processes involved in IRI and summarize the results of our previous preclinical (in vitro and in vivo) DMT studies aiming at mitigating IRI and related cellular neuropathologies. We conclude that the effect of DMT may involve a universal role in cellular protective mechanisms suggesting therapeutic potentials against different components and types of IRIs emerging in local and generalized brain ischemia after stroke or cardiac arrest. The multiple neuroprotective mechanisms facilitated by DMT may position it as a model molecule for developing pharmacological treatments for neurodegenerative disorders.
本文探讨了二甲基色胺(DMT)在神经保护策略中的治疗潜力,特别是在缺血再灌注损伤(IRI)和神经退行性疾病方面。除了其强大的血清素受体作用外,DMT还是sigma-1受体(Sig-1R)的内源性激动剂。Sigma受体是一类独特的蛋白质家族,在脑和脊髓中高表达,并且参与了多种中枢神经系统疾病的病因、症状发展过程及治疗。我们之前的理论和实验工作有力地表明,通过DMT靶向sigma(和血清素)受体可能对治疗多种神经系统疾病特别有用,如中风、全脑缺血、阿尔茨海默病和肌萎缩侧索硬化症。在本文中,我们简要概述了Sig1-R在细胞生物能量学中的功能,重点关注IRI所涉及的过程,并总结了我们之前旨在减轻IRI及相关细胞神经病理学的临床前(体外和体内)DMT研究结果。我们得出结论,DMT的作用可能涉及细胞保护机制中的普遍作用,这表明其对中风或心脏骤停后局部和全身性脑缺血中出现的不同成分和类型的IRI具有治疗潜力。DMT所促进的多种神经保护机制可能使其成为开发神经退行性疾病药物治疗的模型分子。