ArticleCell death & disease2015
Sigma-1 receptor deficiency reduces MPTP-induced parkinsonism and death of dopaminergic neurons.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- Neuromodulatory roles of the sigma-1 receptor in behavior and drug sensitization during development.Acta pharmacologica Sinica · 2026Article
- Role of Sigma-1 Receptors in the Paraventricular Nucleus and Myocardium during Cirrhotic Cardiomyopathy in Rats.Molecular neurobiology · 2026Article
- Mitochondrial Calcium Channels and MAM Interaction in Calcium Homeostasis Dysregulation in Parkinson's Disease.Neurochemical research · 2025Review
- Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.Acta pharmaceutica Sinica. B · 2025Article
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- Behavioral analysis of motor and non-motor impairment in rodent models of Parkinson's disease.Frontiers in aging neuroscience · 2024Review
- Chaperones vs. oxidative stress in the pathobiology of ischemic stroke.Frontiers in molecular neuroscience · 2024Review
- Exploring the Association between Schizophrenia and Cardiovascular Diseases: Insights into the Role of Sigma 1 Receptor.Physiological research · 2023Review
- Sigma-1 receptor and seizures.Pharmacological research · 2023Review
- Blockage of TRPV4 Downregulates the Nuclear Factor-Kappa B Signaling Pathway to Inhibit Inflammatory Responses and Neuronal Death in Mice with Pilocarpine-Induced Status Epilepticus.Cellular and molecular neurobiology · 2023Article
- The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics.Neurochemical research · 2023Review
- Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection.International journal of molecular sciences · 2023Review
- Article
- SIGMAR1 variants in ALS-PD complex cases: a case report of a novel mutation and literature review.Frontiers in neurology · 2023Article
- Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms.International journal of molecular sciences · 2022Review
- Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems.Cellular and molecular neurobiology · 2022Review
- An open-like conformation of the sigma-1 receptor reveals its ligand entry pathway.Nature communications · 2022Article
- Allosteric Modulation of the Sigma-1 Receptor Elicits Antipsychotic-like Effects.Schizophrenia bulletin · 2022Article
- Reduced GFAP Expression in Bergmann Glial Cells in the Cerebellum of Sigma-1 Receptor Knockout Mice Determines the Neurobehavioral Outcomes after Traumatic Brain Injury.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sigma-1 receptor (σ1R) has been reported to be decreased in nigrostriatal motor system of Parkinson's disease patients. Using heterozygous and homozygous σ1R knockout (σ1R+/- and σ1R-/-) mice, we investigated the influence of σ1R deficiency on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-impaired nigrostriatal motor system. The injection of MPTP for 5 weeks in wild-type mice (MPTP-WT mice), but not in σ1R+/- or σ1R-/- mice (MPTP-σ1R+/- or MPTP-σ1R-/- mice), caused motor deficits and ~40% death of dopaminergic neurons in substantia nigra pars compacta with an elevation of N-methyl-d-aspartate receptor (NMDAr) NR2B phosphorylation. The σ1R antagonist NE100 or the NR2B inhibitor Ro25-6981 could alleviate the motor deficits and the death of dopaminergic neurons in MPTP-WT mice. By contrast, MPTP-σ1R+/- mice treated with the σ1R agonist PRE084 or MPTP-σ1R-/- mice treated with the NMDAr agonist NMDA appeared to have similar motor deficits and loss of dopaminergic neurons as MPTP-WT mice. The pharmacological or genetic inactivation of σ1R suppressed the expression of dopamine transporter (DAT) in substantia nigra, which was corrected by NMDA. The activation of σ1R by PRE084 enhanced the DAT expression in WT mice or σ1R+/- mice. By contrast, the level of vesicular monoamine transporter 2 (VMAT2) in σ1R+/- mice or σ1R-/- mice had no difference from WT mice. Interestingly, MPTP-WT mice showed the reduction in the levels of DAT and VMAT2, but MPTP-σ1R-/- mice did not. The inactivation of σ1R by NE100 could prevent the reduction of VMAT2 in MPTP-WT mice. In addition, the activation of microglia cells in substantia nigra was equally enhanced in MPTP-WT mice and MPTP-σ1R-/- mice. The number of activated astrocytes in MPTP-σ1R-/- mice was less than that in MPTP-WT mice. The findings indicate that the σ1R deficiency through suppressing NMDAr function and DAT expression can reduce MPTP-induced death of dopaminergic neurons and parkinsonism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.