The protective effect of DMT against neurodegeneration.

DMT, an endogenous agonist of the sigma-1 receptor (Sig-1R) in addition to its serotonin receptor actions, shows therapeutic potential for neuroprotection against ischemia-reperfusion injury (IRI) and neurodegenerative disorders. Sigma-1 receptors are highly expressed in the brain and spinal cord and are implicated in central nervous system disorders. Previous theoretical and experimental work suggests targeting sigma and serotonin receptors via DMT may treat conditions like stroke, global brain ischemia, Alzheimer's disease, and amyotrophic lateral sclerosis. The paper reviews Sig-1R's role in cellular bioenergetics related to IRI and summarizes preclinical DMT studies that mitigated IRI and related neuropathologies. DMT's effect may involve universal cellular protective mechanisms, positioning it as a model molecule for developing treatments for neurodegenerative disorders.

Study at a glance

Abstract

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.