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Review
. 2024 Dec 30;8(1):47-65.
doi: 10.1021/acsptsci.4c00564. eCollection 2025 Jan 10.

Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders

Mustafa M Shokr  1 , Ghada A Badawi  1 , Shimaa M Elshazly  2 , Hala F Zaki  3 , Ahmed F Mohamed  3   4
Affiliations
Review

Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders

Mustafa M Shokr et al. ACS Pharmacol Transl Sci. .

Abstract

Sigma 1 receptor (S1R) is a multifunctional, ligand-activated protein located in the membranes of the endoplasmic reticulum (ER). It mediates a variety of neurological disorders, including epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease. The wide neuroprotective effects of S1R agonists are achieved by a variety of pro-survival and antiapoptotic S1R-mediated signaling functions. Nonetheless, relatively little is known about the specific molecular mechanisms underlying S1R activity. Many studies on S1R protein have highlighted the importance of maintaining normal cellular homeostasis through its control of calcium and lipid exchange between the ER and mitochondria, ER-stress response, and many other mechanisms. In this review, we will discuss S1R different cellular localization and explain S1R-associated biological activity, such as its localization in the ER-plasma membrane and Mitochondrion-Associated ER Membrane interfaces. While outlining the cellular mechanisms and important binding partners involved in these processes, we also explained how the dysregulation of these pathways contributes to neurodegenerative disorders.

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Conflict of interest statement

The authors declare no competing financial interest.

References

    1. Martin P.; Reeder T.; Sourbron J.; de Witte P. A. M.; Gammaitoni A. R.; Galer B. S. An Emerging Role for Sigma-1 Receptors in the Treatment of Developmental and Epileptic Encephalopathies. Int. J. Mol. Sci. 2021, 22 (16), 8416.10.3390/ijms22168416. - DOI - PMC - PubMed
    1. Salaciak K.; Pytka K. Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders. Neurosci Biobehav Rev. 2022, 132, 1114–1136. 10.1016/j.neubiorev.2021.10.037. - DOI - PMC - PubMed
    1. Siddiqui T.; Bhatt L. K. Targeting Sigma-1 Receptor: A Promising Strategy in the Treatment of Parkinson’s Disease. Neurochem. Res. 2023, 48 (10), 2925–2935. 10.1007/s11064-023-03960-6. - DOI - PMC - PubMed
    1. Hanner M.; Moebius F. F.; Flandorfer A.; Knaus H. G.; Striessnig J.; Kempner E.; Glossmann H. Purification, molecular cloning, and expression of the mammalian sigma1-binding site. Proc. Natl. Acad. Sci. U. S. A. 1996, 93 (15), 8072–7. 10.1073/pnas.93.15.8072. - DOI - PMC - PubMed
    1. Aydar E.; Palmer C. P.; Klyachko V. A.; Jackson M. B. The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron 2002, 34 (3), 399–410. 10.1016/S0896-6273(02)00677-3. - DOI - PubMed