The Intriguing Sigma-1 and Sigma-2 Receptors and Their Potential Therapeutic Roles 2.0 DOI Open Access
Carmen Abate, Tangui Maurice

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15868 - 15868

Published: Nov. 1, 2023

For some time now, the research on sigma receptors has been at a high level of maturity but, despite everything that already achieved, further work in this field still holds huge appeal, with vast possibilities for original discoveries [...]

Language: Английский

Astrocyte-specific activation of sigma-1 receptors in mPFC mediates the faster onset antidepressant effect by inhibiting NF-κB-induced neuroinflammation DOI
Jingya Wang, Peng Ren,

Lin-Yu Cui

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 120, P. 256 - 274

Published: June 8, 2024

Language: Английский

Citations

9
Current landscape of fecal microbiota transplantation in treating depression DOI Creative Commons
Qi Zhang,

Yajun Bi,

Boyu Zhang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 25, 2024

Depression, projected to be the predominant contributor global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication psychotherapy often fall short, prompting pursuit of alternative interventions. Recent research has highlighted significant role gut microbiota in mental health, influencing emotional neural regulation. Fecal transplantation (FMT), infusion fecal matter from healthy donor into patient, emerges promising strategy ameliorate depressive by restoring microbial balance. The microbial-gut-brain (MGB) axis represents critical pathway through which potentially rectify dysbiosis modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals reduce inflammatory markers, thereby alleviating behaviors. Moreover, shown promise clinical settings, improving gastrointestinal overall quality life patients depression. review highlights gut-brain depression need for further validate long-term safety efficacy FMT, identify specific therapeutic strains, develop targeted modulation strategies. Advancing our understanding could revolutionize treatment, shifting paradigm toward microbiome-targeting therapies.

Language: Английский

Citations

7
Berberine ameliorates seizure activity and cardiac dysfunction in pentylenetetrazol-kindling seizures in rats: Modulation of sigma1 receptor, Akt/eNOS signaling, and ferroptosis DOI

Shrouk M Basiouny,

Hala F. Zaki,

Shimaa M. Elshazly

et al.

Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110295 - 110295

Published: Jan. 1, 2025

Language: Английский

Citations

0
Enhancement of neurogenesis and antidepressant-like efficacy through combined activation of Sigma-1 and 5-HT1A receptors: focus on Sigma-1-5-HT1A heteroreceptor complex DOI
Peng Ren, Jingya Wang,

Mengjie Xu

et al.

Neurochemistry International, Journal Year: 2025, Volume and Issue: unknown, P. 105937 - 105937

Published: Jan. 1, 2025

Language: Английский

Citations

0
Novel Emopamil-Binding Protein Inhibitors for Treating Multiple Sclerosis DOI
Ram W. Sabnis

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

Citations

0
Exploring the Relationship Between Antipsychotic Drug Target Genes and Epilepsy: Evidence From Food and Drug Administration Adverse Event Reporting System Database and Mendelian Randomization DOI Creative Commons
Ziqian Yin, Zheng Zhan,

Youjia Qiu

et al.

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(4)

Published: April 1, 2025

ABSTRACT Background The effect of antipsychotic drugs on epilepsy is controversial, and we performed Food Drug Administration Adverse Event Reporting System (FAERS) data mining Mendelian Randomization (MR) analyses to clarify the effects target genes epilepsy. Method We explored antipsychotic‐induced AE signals in FAERS. Gene expression was obtained from eQTLGen consortium GTEx project. Epilepsy were FinnGen International League Against (ILAE). MR, Summary‐data‐based (SMR), colocalization analysis sequentially performed, meta‐analysis with significant MR or SMR assess causal relationship between them Result Through FAERS database mining, 63 antipsychotics reported 5121 adverse events identified potential associations 14 drug for its subtypes. MCHR1 SIGMAR1 still after no evidence heterogeneity pleiotropy. showed that DRD4 ADRA1D strongly associated subtypes however, neither gene passed HEIDI test. Conclusion Our study indicates are a high incidence epilepsy‐related AEs. demonstrated targets Providing new insights managing patients psychiatric disorders.

Language: Английский

Citations

0
Navigating the future of retinitis pigmentosa treatments: A comprehensive analysis of therapeutic approaches in rd10 mice DOI Creative Commons
Hongli Yang, Hui Zhang, Xiaorong Li

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 193, P. 106436 - 106436

Published: Feb. 8, 2024

Retinitis pigmentosa (RP) is a degenerative disease, caused by genetic mutations that lead to loss in photoreceptors. For research on RP, rd10 mice, which carry the phosphodiesterase (PDE) gene, exhibit patterns comparable those of patients with making them an ideal model for investigating potential treatments. Although numerous studies have reported biochemical drugs, gene correction, and stem cell transplantation decelerating retinal degeneration, comprehensive review these has yet be conducted. Therefore, here, comparative analysis mouse treatment over past decade was performed. Our findings suggest drugs capable inhibiting inflammatory response may promising therapeutics. Additionally, significant progress been made field therapy; nevertheless, challenges such as strict delivery requirements, bystander editing, off-target effects still need resolved. Nevertheless, secretory function only unequivocal protective effect transplantation. In summary, this presents synthesis approaches employing mice experimental subjects, describing clear pathway future RP identifies clinical interventions.

Language: Английский

Citations

3
The classical D1 dopamine receptor antagonist SCH23390 is a functional sigma-1 receptor allosteric modulator DOI

Gu-fang Zhang,

Kailian Zhu,

Qi Li

et al.

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: 45(8), P. 1582 - 1590

Published: April 11, 2024

Language: Английский

Citations

2
The Protective Role of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Protein Sigma-1 Receptor in Regulating Endothelial Inflammation and Permeability Associated with Acute Lung Injury DOI Creative Commons

Zahra Mahamed,

Mohammad Shadab, Rauf Ahmad Najar

et al.

Cells, Journal Year: 2023, Volume and Issue: 13(1), P. 5 - 5

Published: Dec. 19, 2023

Earlier studies from our lab identified endoplasmic reticulum (ER) chaperone BiP/GRP78, an important component of MAM, to be a novel determinant endothelial cell (EC) dysfunction associated with acute lung injury (ALI). Sigma1R (Sig1R) is another unique ER receptor that has been associate BiP/GRP78 at the MAM and known pluripotent modulator cellular homeostasis. However, it unclear if Sig1R also plays role in regulating EC inflammation permeability ALI. Our data using human pulmonary artery cells (HPAECs) showed siRNA-mediated knockdown potentiated LPS-induced expression proinflammatory molecules ICAM-1, VCAM-1 IL-8. Consistent this, agonist, PRE-084, activate by inducing its dissociation blunted above response. Notably, PRE-084 failed blunt inflammatory responses Sig1R-depleted cells, confirming effect driven Sig1R. Furthermore, antagonist, NE-100, inactivate blocking block responses, establishing required for exert anti-inflammatory action. Unlike Sig1R, or Subtilase AB-mediated inactivation protected against inflammation. Interestingly, protective was abolished were depleted knockdown/inactivation-mediated suppression mediated via In view these findings, we determined vivo relevance mouse model sepsis-induced The intraperitoneal injection mitigated ALI, as evidenced decrease IL-6 levels, PMN infiltration, vascular leakage. Together, evidence ALI identify viable target terms controlling sepsis.

Language: Английский

Citations

6
The Psychedelic N,N-Dipropyltryptamine Prevents Seizures in a Mouse Model of Fragile X Syndrome via a Mechanism that Appears Independent of Serotonin and Sigma1 Receptors DOI Creative Commons
Richa Tyagi, Tanishka S. Saraf, Clinton E. Canal

et al.

ACS Pharmacology & Translational Science, Journal Year: 2023, Volume and Issue: 6(10), P. 1480 - 1491

Published: Sept. 18, 2023

The serotonergic psychedelic psilocybin shows efficacy in treating neuropsychiatric disorders, though the mechanism(s) underlying its therapeutic effects remain unclear. We show that a similar tryptamine, N,N-dipropyltryptamine (DPT), completely prevents audiogenic seizures (AGS) an Fmr1 knockout mouse model of fragile X syndrome at 10 mg/kg dose but not lower doses (3 or 5.6 mg/kg). Despite showing vitro DPT is serotonin 5-HT2A, 5-HT1B, and 5-HT1A receptor agonist (with rank order functional potency, determined with TRUPATH Gα/βγ biosensors), pretreatment selective inhibitors 5-HT2A/2C, receptors did block DPT's antiepileptic effects; pan-serotonin antagonist was also ineffective. Because activation blocks AGS mice, we performed dose–response experiment to evaluate engagement vivo. elicited 5-HT1A-dependent only greater than mg/kg, further supporting were 5-HT1A-mediated. observed sigma1 antagonist, NE-100, impact effects, suggesting crucial mechanism. Separately, NE-100 high caused convulsions on their own qualitatively distinct from AGS. In conclusion, dose-dependently blocked neither nor antagonists prevented this action. Thus, might have neurotherapeutic independent properties. However, doses, has complex dose-dependent vivo polypharmacology.

Language: Английский

Citations

3