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Sigma-1 Receptor in Motoneuron Disease
2017Amyotrophic Lateral Sclerosis (ALS ) is a neurodegenerative disease affecting spinal cord and brain motoneurons , leading to paralysis and early death. Multiple etiopathogenic mechanisms appear to contribute in the development of ALS , including glutamate excitotoxicity, oxidative stress , protein misfolding, mitochondrial defects, impaired axonal ...
Mancuso, Renzo, Navarro, Xavier
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Sigma-1 Receptor and Neuronal Excitability
2017The sigma-1 receptor (Sig-1R), via interaction with various proteins, including voltage-gated and ligand-gated ion channels (VGICs and LGICs), is involved in a plethora of neuronal functions. This capability to regulate a variety of ion channel targets endows the Sig-1R with a powerful capability to fine tune neuronal excitability, and thereby the ...
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Structural Perspectives on Sigma-1 Receptor Function
2017The sigma-1 receptor is an enigmatic ER-resident transmembrane protein linked to a variety of human diseases. Although the receptor was first cloned 20 years ago, the molecular structure of the protein and the mechanistic basis for its interaction with drug-like small molecules have remained unclear until recently.
Assaf, Alon +3 more
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The Sigma-1 Receptor at the Crossroad of Proteostasis, Neurodegeneration, and Autophagy
Trends in Neurosciences, 2020Neurodegenerative diseases are linked to dysfunctional proteostasis and disturbed autophagy. Here, we discuss how the sigma-1 receptor (Sig-1R) may act at the intersection of this interaction, as loss-of-function mutations of this unique chaperone are associated with defective autophagy and its pharmacological activation induces autophagic activity.
Maximilian G, Christ +2 more
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Sigma-1 receptor and amyotrophic lateral sclerosis
Neurology, 2018Sigma-1 receptor (Sig-1R, σ1R, also referred to as sigma receptor 1, SigR1) is an endoplasmic reticulum (ER) protein that is specifically located at the mitochondria-associated ER membrane (MAM), which interfaces between the ER and mitochondria. At the level of MAM, Sig-1R functions as a molecular chaperone that ensures proper calcium (Ca2+) transfer ...
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The Sigma-1 Receptor—Orphan No More
Science Signaling, 2009An endogenous compound is a ligand for a ubiquitously expressed receptor that binds many synthetic drugs and has been implicated in psychiatric disease.
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SKF83959 Is a Potent Allosteric Modulator of Sigma-1 Receptor
Molecular Pharmacology, 2013SKF83959 (3-methyl-6-chloro-7,8-hydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine), an atypical dopamine receptor-1 (D(1) receptor) agonist, has shown many D(1) receptor-independent effects, such as neuroprotection, blockade of Na(+) channel, and promotion of spontaneous glutamate release, which resemble the effects of the sigma-1 receptor
Lin, Guo +6 more
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Investigational sigma-1 receptor antagonists for the treatment of pain
Expert Opinion on Investigational Drugs, 2015The sigma-1 receptor (σ1R) is a ligand-regulated molecular chaperone that interacts with other proteins, including NMDA and opioid receptors, to modulate their activity. Convergent evidence indicates that σ1R antagonists exert inhibitory effects (and agonists stimulatory effects) on pain by stepping down the intracellular signaling cascades involved in
José Miguel, Vela +2 more
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Probing the proposed phenyl-A region of the sigma-1 receptor
Bioorganic & Medicinal Chemistry, 2002The proposed phenyl-A region of sigma (sigma) receptors accommodates several structural features. In this study we explored the possibility that appropriate structural features located at the phenyl-A region of sigma receptor sites could lead to more potent and selective agents for the sigma receptor subtypes. By keeping the phenyl-B substituent as the
Seth Y, Ablordeppey +3 more
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The Role of Sigma 1 Receptor as a Neuroprotective Target in Glaucoma
2017The role of sigma 1 receptor (S1R) in glaucoma is emerging as a promising field of study. Glaucoma is an optic neuropathy that shares common pathogenic mechanisms with other neurodegenerative diseases such as Alzheimer's and Parkinson's disease . S1R modulates multiple cellular functions associated with neurodegeneration .
Barbara, Mysona +3 more
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