Multitargeting in cardioprotection: An example of biaromatic compounds DOI
Г. В. Мокров

Archiv der Pharmazie, Journal Year: 2023, Volume and Issue: 356(9)

Published: June 22, 2023

Abstract A multitarget drug design approach is actively developing in modern medicinal chemistry and pharmacology, especially with regard to multifactorial diseases such as cardiovascular diseases, cancer, neurodegenerative diseases. detailed study of many well‐known drugs developed within the single‐target also often reveals additional mechanisms their real pharmacological action. One approaches can be identification basic pharmacophore models corresponding a wide range required target ligands. Among group cardioprotectors linked biaromatic system. This review develops concept “basic pharmacophore” using an example. It presents analysis possible biological targets for compounds spectrum five most known studied cardioprotective this model, involvement effects these drugs.

Language: Английский

Calcium signaling crosstalk between the endoplasmic reticulum and mitochondria, a new drug development strategies of kidney diseases DOI

Wen-Di Ge,

Tian-Tian Du,

Cao-Yang Wang

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 225, P. 116278 - 116278

Published: May 11, 2024

Language: Английский

Citations

5
Afobazole alleviates streptozotocin-induced diabetic nephropathy in rats via hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties: Role of the S1R/Nrf2 antioxidant axis DOI
Alaa S. Wahba,

Dalia M. Asal,

Noha M. Mesbah

et al.

Life Sciences, Journal Year: 2025, Volume and Issue: 363, P. 123410 - 123410

Published: Jan. 20, 2025

Language: Английский

Citations

0
SA4503 Mitigates Adriamycin-Induced Nephropathy via Sigma-1 Receptor in Animal and Cell-Based Models DOI Creative Commons

Hideaki Tagashira,

Shinsuke Chida,

Md. Shenuarin Bhuiyan

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 172 - 172

Published: Jan. 27, 2025

Background/Objectives: The Sigma-1 receptor (Sigmar1), an intracellular chaperone protein, is ubiquitously expressed throughout the body, but its role in peripheral organs, such as kidneys, remains unclear. Here, we investigated protective effects and molecular mechanisms of SA4503, a selective Sigmar1 agonist, on Adriamycin (ADR)-induced renal glomerular injury. Methods: Using vitro vivo models, evaluated SA4503 ADR-induced podocyte injury, including survival, albumin permeability, urinary levels, Sigmar1-nephrin interactions. NE-100, antagonist, was co-administered to validate specificity SA4503. Results: highly podocytes mouse kidney tissues. significantly reduced injury leakage mice. Mechanistically, preserved interactions, which were disrupted ADR-treated kidneys. This effect abolished by NE-100 co-treatment, confirming Sigmar1-dependency SA4503’s action. Conclusions: These findings demonstrate that activation protects against damage, likely stabilizing Therefore, represents promising therapeutic target for diseases nephrotic syndrome.

Language: Английский

Citations

0
Targeting the sigma-1 receptor with pridopidine induces functional neurorestoration in spinal cord ischemia-reperfusion injury DOI Creative Commons
Eman Sweed, Suzan A Khodir, Shaimaa M. Motawea

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Language: Английский

Citations

0
Potential Role of Sigma-1 Receptor Inhibition and ER Stress-Related Pathways in Upregulating Definitive Endoderm Markers in Human Embryonic Stem cells DOI

Elmira Rezaei Zonooz,

Zahra Ghezelayagh,

Azadeh Moradmand

et al.

Experimental Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 114557 - 114557

Published: April 1, 2025

Language: Английский

Citations

0
SIGMAR1 targets AMPK/ULK1 pathway to inhibit SH-SY5Y cell apoptosis by regulating endoplasmic reticulum stress and autophagy DOI
Min Kong, Zhiheng Chen, Zhiqiang Lin

et al.

Functional & Integrative Genomics, Journal Year: 2024, Volume and Issue: 24(4)

Published: Aug. 1, 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
Blocking Sigmar1 exacerbates methamphetamine-induced hypertension DOI Creative Commons
Zhenzhen Xu, Jie Zhou,

Ke Duan

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(7), P. 167284 - 167284

Published: June 7, 2024

Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced remain unclear. Therefore, we aimed to reveal potential underlying hypertension.

Language: Английский

Citations

1
Targeting endoplasmic reticulum stress as a potential therapeutic strategy for diabetic cardiomyopathy DOI Creative Commons
Irem Congur, Geltrude Mingrone, Kaomei Guan

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 162, P. 156062 - 156062

Published: Nov. 6, 2024

Language: Английский

Citations

1
Exploring the Association between Schizophrenia and Cardiovascular Diseases: Insights into the Role of Sigma 1 Receptor DOI Creative Commons

J Rafcikova,

M. Nováková,

Tibor Stračina

et al.

Physiological Research, Journal Year: 2023, Volume and Issue: unknown, P. S113 - S126

Published: July 31, 2023

Contemporary society is characterized by rapid changes. Various epidemiological, political and economic crises represent a burden to mental health of nowadays population, which may at least partially explain the increasing incidence disorders, including schizophrenia. Schizophrenia associated with premature mortality 13–15 years. The leading cause in schizophrenia patients high cardiovascular diseases. specific-cause risk for diseases more than twice higher as compared general population. Several factors are discussed factor development. Intensive efforts identify possible link between made. It seems that sigma 1 receptor such link. By modulation activity several neurotransmitter systems, dopamine, glutamate, GABA, might play role pathophysiology Moreover, significant roles system have been repeatedly reported. detailed both disorders development however remains unclear. article presents an overview current knowledge about association proposes explanations special emphasis on receptor.

Language: Английский

Citations

2