Abstract
Sigma-1 receptor (Sig-1R) is a protein present in several organs such as brain, lung, and heart. In a cell, Sig-1R is mainly located across the membranes of the endoplasmic reticulum and more specifically at the mitochondria-associated membranes. Despite numerous studies showing that Sig-1R could be targeted to rescue several cellular mechanisms in different pathological conditions, less is known about its fundamental relevance. In this review, we report results from various studies and focus on the importance of Sig-1R in physiological conditions by comparing Sig-1R KO mice to wild-type mice in order to investigate the fundamental functions of Sig-1R. We note that the Sig-1R deletion induces cognitive, psychiatric, and motor dysfunctions, but also alters metabolism of heart. Finally, taken together, observations from different experiments demonstrate that those dysfunctions are correlated to poor regulation of ER and mitochondria metabolism altered by stress, which could occur with aging.
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Abbreviations
- AAV:
-
Adeno-associated virus
- ACTH:
-
Adrenocorticotropic hormone
- AD:
-
Alzheimer’s disease
- Ala:
-
Alamine
- ALS:
-
Amyotrophic lateral sclerosis
- AMRS:
-
Acute mild restraint stress
- ATP:
-
Adenosine triphosphate
- BiP:
-
Binding immunoglobulin protein
- CA1:
-
Cornu Ammonis 1
- cAMP:
-
Cyclic adenosine monophosphate
- CD1:
-
Capsaicin sensitized
- CNS:
-
Central nervous system
- CPS1:
-
Carbamoyl phosphate synthetase I
- CREB:
-
cAMP response element-binding protein
- CRF:
-
Corticotropin-releasing factor
- DG:
-
Dentate gyrus
- DMT:
-
N,N-dimethyltryptamine
- DRG:
-
Dorsal root ganglion
- eGFP:
-
Enhanced GFP
- ERK1/2:
-
Extracellular signal-regulated kinases 1 and 2
- FST:
-
Forced swim test
- GFP:
-
Green fluorescent protein
- Gln:
-
Glutamine
- Glu:
-
Glutamic acid
- GRP78:
-
78-kDa glucose-regulated protein
- GSSG:
-
Oxidized glutathione
- HD:
-
Huntington’s disease
- HPA:
-
Hypothalamic pituitary adrenal
- HSP5:
-
Heat shock protein 5
- IP3R:
-
Inositol trisphosphate receptor
- IRE1:
-
Inositol-requiring enzyme 1
- KD:
-
Knockdown
- KO:
-
Knockout
- MAM:
-
Mitochondria-associated membranes
- mRNA:
-
Messenger RNA
- Mups:
-
Major urinary proteins
- NMDA:
-
N-methyl-d-aspartate
- NMDAr:
-
NMDA receptor
- NR2B:
-
NMDA receptor subtype 2B
- OVX:
-
Ovariectomizing
- PD:
-
Parkinson’s disease
- pERK1/2:
-
Phosphorylated ERK1/2
- PET:
-
Positron emission tomography
- PKA:
-
Protein kinase A
- PKC:
-
Protein kinase C
- PMA:
-
Phorbol 12-myristate 13-acetate
- PP2:
-
4-Amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine
- Prdx6:
-
Peroxiredoxin-6
- PSNL:
-
Partial sciatic nerve ligation
- PVN:
-
Paraventricular nucleus of the hypothalamus
- ROS:
-
Reactive oxygen speices
- SCI:
-
Spinal cord contusion injury
- Sig-1R:
-
Sigma-1 receptor
- SKF:
-
Alazocine
- STPA:
-
Step-through passive avoidance
- Thr:
-
Threonine
- TRPV1:
-
Transient receptor potential cation channel, subfamily V, member 1
- TST:
-
Tail suspension test
- Val:
-
Valine
- WT:
-
Wild-type
- XBP1:
-
X-box binding protein 1
- YMT:
-
Y-maze test
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This research was supported by the Intramural Research Program of the National Institute on Drug Abuse and the National Institutes of Health. We would also like to thank Dr. Mary Pfeiffer and Dr. Jean-Charles Lievens for their corrections.
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The authors were supported by the Intramural research program NIDA, NIH/DHHS.
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Couly, S., Goguadze, N., Yasui, Y. et al. Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems. Cell Mol Neurobiol 42, 597–620 (2022). https://doi.org/10.1007/s10571-020-00983-3
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DOI: https://doi.org/10.1007/s10571-020-00983-3