Cognitive impairment in endocrine and metabolic disorders: the role of sigma-1 receptors and the potential of pyrrole derivatives

Abstract

In today’s global population aging environment cognitive impairment appears to be increasingly prevalent and become one of the leading causes of disability and mortality in the world. Increasing life expectancy is accompanied by more frequent occurrence of neurodegenerative and metabolically provoked lesions of the central nervous system. In addition to age-related changes, endocrine pathology plays a significant role in the development of cognitive deficiency. This pathology includes diabetes mellitus, thyroid diseases, metabolic syndrome and adrenal pathology. Key pathogenic mechanisms are oxidative stress, neurological inflammation, calcium homeostasis disturbances, endothelial dysfunction and mitochondrial disorders. Sigma-1 receptors (S1R) are of special attention in current studies. They perform the function of intracellular chaperones and regulate a wide range of neural processes including neuroplasticity, synaptic transmission and cellular homeostasis. S1R activation is associated with neuroprotective effects, decrease of neurological inflammation and improvement of cognitive functions. Pyrrole derivatives as potential S1R ligands are considered among the promising areas of pharmacotherapy. They combine antioxidant, anti-inflammatory and neuroprotective properties. Modern S1R agonists including Pridopidine, Blarcamesine and Dimethyltryptamine in particular, are of special interest. They demonstrate positive results in preclinical and clinical studies. Therefore, targeting of Sigma-1 receptors is a promising approach to the development of new effective means for the correction of cognitive impairment, especially in patients with metabolic and endocrine disorders.