Abstract
The sigma-1 receptor (Sig-1R) is encoded by the SIGMAR1 gene and is a nonopioid transmembrane receptor located in the mitochondrial-associated endoplasmic reticulum membrane (MAM). It helps to locate endoplasmic reticulum calcium channels, regulates calcium homeostasis, and acts as a molecular chaperone to control cell fate and participate in signal transduction. It plays an important role in protecting neurons through a variety of signaling pathways and participates in the regulation of cognition and motor behavior closely related to neurodegenerative diseases. Based on its neuroprotective effects, Sig-1R has now become a breakthrough target for alleviating Alzheimer’s disease and other neurodegenerative diseases. This article reviews the most cutting-edge research on the function of Sig-1R under normal or pathologic conditions and target drugs of the sigma-1 receptor in neurodegenerative diseases.
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Abbreviations
- Sig-1R:
-
Sigma-1 receptor
- MAM:
-
Mitochondrial-associated endoplasmic reticulum membrane
- CHOP:
-
C/EBP homologous protein
- DHEA:
-
Dehydroepiandrosterone
- DHEAS:
-
DHEA sulfate
- Znf179:
-
Zinc finger protein 179
- ROS:
-
Reactive oxygen species
- iNOS:
-
Inducible nitric oxide synthase
- TNF-α:
-
Tumor necrosis factor-alpha
- GSH:
-
Glutathione
- Nrf2:
-
Erythroid-derived nuclear factor-related factor-2
- HO-1:
-
Heme oxygenase-1
- ERK1/2:
-
Extracellular signal-regulated kinase 1/2
- GSK3β:
-
Glycogen synthase kinase 3β
- NGF:
-
Nerve growth factor
- TrkB:
-
Tropomyosin receptor kinase B
- NMDAR:
-
N-methyl-D-aspartate receptors
- HD:
-
Huntington’s disease
- HTT:
-
Huntingtin gene
- iPSC:
-
Induce pluripotent stem cells
- AD:
-
Alzheimer’s disease
- Aβ:
-
Amyloid β peptide
- PD:
-
Parkinson’s disease
- ALS:
-
Amyotrophic lateralizing sclerosis
- GR:
-
Glucocorticoid receptor
- dHMNs:
-
Distal hereditary motor neuropathy
- RTT:
-
Rett syndrome
- ONHAs:
-
Optic nerve head-derived astrocytes
- PKC:
-
Protein kinase C
- 2-AG:
-
2-Arachidonic acid glyceride
- ARF6:
-
ADP ribosylation factor
- PKB:
-
Protein kinase B
- eNOS:
-
Endothelial nitric oxide synthase
- FTH1:
-
Ferritin heavy chain 1
- TFR1:
-
Transferrin receptor protein 1
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We thank Chao Liu for her help in manuscript revision.
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This work was supported by the National Natural Science Foundation of China (81870173), Young Talent Project of Hubei Provincial Health and Health Committee (WJ2019Q013), Scientific Research Plan of Hubei Provincial Department of Education (D20202803), Natural Science Foundation of Hubei Province (2020CFB851), and Hubei University of Science and Technology School-level Fund (No.2020XZ13, BK202009).
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Ning-hua Wu and Yu Ye edited and wrote the manuscript. Bin-bin Wan and Yuan-dong Yu revised and participated in the discussion of the manuscript. Chao Liu and Qing-Jie Chen participated in the manuscript design and coordination. All authors read and approved the final manuscript.
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Wu, Nh., Ye, Y., Wan, Bb. et al. Emerging Benefits: Pathophysiological Functions and Target Drugs of the Sigma-1 Receptor in Neurodegenerative Diseases. Mol Neurobiol 58, 5649–5666 (2021). https://doi.org/10.1007/s12035-021-02524-5
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DOI: https://doi.org/10.1007/s12035-021-02524-5