The Intriguing Sigma-1 and Sigma-2 Receptors and Their Potential Therapeutic Roles 2.0

Dear Colleagues,

Almost five decades after their discovery, the role of sigma receptors in health and disease is still an intriguing subject. The sigma-1 subtype has been defined as a pluripotent chaperone that interacts with several client proteins. Its recently obtained crystal structure, which shows a peculiar folding, will facilitate the understanding of the oligomerization/polymerization processes that address the sigma-1 receptor functions. Drugs interacting with the sigma-1 subtype have potential for the treatment of CNS disfunctions, neurodegenerative diseases, pain, cocaine abuse, and tumors. After diverse hypotheses, the sigma-2 subtype was recently identified as TMEM97, rejuvenating interest in sigma-2-related research. The overexpression of this subtype in tumor tissues and its role in cell proliferation have mostly driven the research in the oncology field, but recent evidence has highlighted sigma-2 as the receptor responsible for the binding of Abeta oligomers to neurons; one sigma-2 ligand is now in clinical trials for the treatment of Alzheimer’s disease. Surprisingly, sigma receptors have been identified as host proteins for interaction with SARS-CoV-2 proteins, with one sigma ligand performing 20-fold better than hydroxychloroquine in the antiviral assays.

This Special Issue will collect data from the experts in the sigma receptor field with the aim of disseminating knowledge about these pluripotent proteins and advancing research toward their full understanding and possible therapeutic applications.

Dr. Tangui Maurice
Dr. Carmen Abate
Guest Editors

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