Emerging Benefits: Pathophysiological Functions and Target Drugs of the Sigma-1 Receptor in Neurodegenerative Diseases

• Published in: Molecular neurobiology Vol. 58; no. 11; pp. 5649 - 5666
• Main Authors: Wu, Ning-hua, Ye, Yu, Wan, Bin-bin, Yu, Yuan-dong, Liu, Chao, Chen, Qing-jie
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-11-2021; Springer Nature B.V
• Subjects: Alzheimer's disease; Animals; Autophagy; Biomedical and Life Sciences; Biomedicine; Bulimia - drug therapy; Bulimia - physiopathology; Calcium (reticular); Calcium - metabolism; Calcium channels; Calcium homeostasis; Cell Biology; Cell fate; Cognition; Cognition - drug effects; Depressive Disorder - drug therapy; Depressive Disorder - physiopathology; Drug Evaluation, Preclinical; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Homeostasis; Humans; Ion Channels - metabolism; Membrane Microdomains; Mitochondria; Motor Activity - drug effects; Nerve Growth Factors - biosynthesis; Nerve Tissue Proteins - agonists; Nerve Tissue Proteins - physiology; Neuralgia - drug therapy; Neuralgia - physiopathology; Neurobiology; Neurodegenerative diseases; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - physiopathology; Neurology; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Oxidative Stress; Rats; Receptors, sigma - agonists; Receptors, sigma - physiology; Retinal Degeneration - drug therapy; Retinal Degeneration - physiopathology; Sigma-1 Receptor; Signal transduction; Substance-Related Disorders - drug therapy; Substance-Related Disorders - physiopathology; Unfolded Protein Response; MAM; Neurodegenerative; Sigma-1 receptor; Target drugs; SIGMAR1
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-021-02524-5

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.