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At the Crossing of ER Stress and MAMs: A Key Role of Sigma-1 Receptor?

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Calcium Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1131))

Abstract

Calcium exchanges and homeostasis are finely regulated between cellular organelles and in response to physiological signals. Besides ionophores, including voltage-gated Ca2+ channels, ionotropic neurotransmitter receptors, or Store-operated Ca2+ entry, activity of regulatory intracellular proteins finely tune Calcium homeostasis. One of the most intriguing, by its unique nature but also most promising by the therapeutic opportunities it bears, is the sigma-1 receptor (Sig-1R). The Sig-1R is a chaperone protein residing at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), where it interacts with several partners involved in ER stress response, or in Ca2+ exchange between the ER and mitochondria. Small molecules have been identified that specifically and selectively activate Sig-1R (Sig-1R agonists or positive modulators) at the cellular level and that also allow effective pharmacological actions in several pre-clinical models of pathologies. The present review will summarize the recent data on the mechanism of action of Sig-1R in regulating Ca2+ exchanges and protein interactions at MAMs and the ER. As MAMs alterations and ER stress now appear as a common track in most neurodegenerative diseases, the intracellular action of Sig-1R will be discussed in the context of the recently reported efficacy of Sig-1R drugs in pathologies like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, or amyotrophic lateral sclerosis.

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Authors and Affiliations

  1. MMDN, University of Montpellier, EPHE, INSERM, U1198, Montpellier, France

    Benjamin Delprat, Lucie Crouzier & Tangui Maurice

  2. Cellular Pathobiology Section, Integrative Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, IRP, NIDA/NIH, Baltimore, MD, USA

    Tsung-Ping Su

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  4. Tangui Maurice
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Correspondence to Benjamin Delprat .

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    Md. Shahidul Islam

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Delprat, B., Crouzier, L., Su, TP., Maurice, T. (2020). At the Crossing of ER Stress and MAMs: A Key Role of Sigma-1 Receptor?. In: Islam, M. (eds) Calcium Signaling. Advances in Experimental Medicine and Biology, vol 1131. Springer, Cham. https://doi.org/10.1007/978-3-030-12457-1_28

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