Sigma-1 receptor agonists as potential protective therapies in multiple sclerosis

Robert P Lisak; Liljana Nedelkoska; Joyce A Benjamins

doi:10.1016/j.jneuroim.2020.577188

Sigma-1 receptor agonists as potential protective therapies in multiple sclerosis

J Neuroimmunol. 2020 Feb 21:342:577188. doi: 10.1016/j.jneuroim.2020.577188. Online ahead of print.

Authors

Robert P Lisak¹, Liljana Nedelkoska², Joyce A Benjamins³

Affiliations

¹ Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: rlisak@med.wayne.edu.
² Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: lnedelk@med.wayne.edu.
³ Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: jbenjami@med.wayne.edu.

PMID: 32179326
DOI: 10.1016/j.jneuroim.2020.577188

Abstract

The sigma-1 receptor (σ-1R) is an endoplasmic reticulum (ER) chaperone upregulated during ER stress, and regulates calcium homeostasis. Agonists of σ-1R are neuroprotective. ANAVEX2-73, a new σ-1R agonist, is undergoing several clinical trials. We show that ANAVEX2-73 protects oligodendroglia (OL) and oligodendroglial precursors (OPC) from apoptosis, excitotoxicity, reactive oxygen species (ROS) and quinolinic acid (QA), associated with inflammation. ANAVEX2-73 stimulates OPC proliferation, but does not alter early maturation to OL. We previously reported that dextromethorphan (DM), another σ-1R agonist with a different structure, had similar effects. We now show that both DM and ANAVEX2-73 protect neurons from the four cytotoxic agents.