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Last update 23 Jan 2025

RORγ1

Last update 23 Jan 2025

Basic Info

Synonyms-

Introduction-

Drugs associated with RORγ1

SR-1078

Target

RORα x RORγ1

Mechanism

RORα inhibitors [+1]

Active Org.

Xinhua Hospital

Originator Org.

Xinhua Hospital

Active Indication

Pancreatitis, Chronic

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with RORγ1

100 Translational Medicine associated with RORγ1

0 Patents (Medical) associated with RORγ1

Literatures (Medical) associated with RORγ1

01 Jan 2025·International Immunopharmacology

Canagliflozin attenuates neurodegeneration and ameliorates dyskinesia through targeting the NLRP3/Nurr1/GSK-3β/SIRT3 pathway and autophagy modulation in rotenone-lesioned rats

Article

Author: Salem, Hesham A ; Abdelaziz, Ahmed M ; Rasheed, Nora O Abdel ; Zaki, Hala F ; El-Sayed, Rehab M

Despite a deep understanding of Parkinson's disease (PD) and levodopa-induced dyskinesia (LID) pathogenesis, current therapies are insufficient to effectively manage the progressive nature of PD or halt LID. Growing hypotheses suggested the NOD-like receptor 3 (NLRP3) inflammasome and orphan nuclear receptor-related 1 (Nurr1)/glycogen synthase kinase-3β (GSK-3β) and peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α)/sirtuin 3 (SIRT3) pathways as potential avenues for halting neuroinflammation and oxidative stress in PD.AIMSThis study investigated for the first time the neuroprotective effect of canagliflozin against PD and LID in rotenone-intoxicated rats, emphasizing the crosstalk among the NLRP3/caspase-1 cascade, PGC-1α/SIRT3 pathway, mammalian target of rapamycin (mTOR)/beclin-1, and Nurr1/β-catenin/GSK-3β pathways as possible treatment strategies in PD and LID. Also, correlating NLRP3 expression with all evaluated parameters.MAIN METHODSThe PD rat model was induced via eleven rotenone (1.5 mg/kg) subcutaneous injections day after day. Canagliflozin (20 mg/kg) and/or L-dopa/carbidopa (100/25 mg/kg) were orally administered daily from the beginning until the end of the experiment.KEY FINDINGSCanagliflozin significantly improved neurobehavioral and histological assessments, whereas dyskinesia scores declined. The improvement was confirmed through tyrosine hydroxylase and β-catenin upregulation in contrast to NLRP3 and caspase-1 in substantia nigra pars compacta, as revealed immunohistochemically. In addition, canagliflozin induced a prominent elevation in dopamine, Nurr1, PGC-1α, SIRT3, and beclin-1, whereas mTOR and GSK-3β expressions were downregulated.SIGNIFICANCEOur results revealed the aspiring canagliflozin neuroprotective properties against PD and LID in rotenone-lesioned rats via the assumed anti-inflammatory activity and implication of NLRP3/caspase-1, Nurr1/GSK-3β/β-catenin, PGC-1α/SIRT3, and beclin-1/mTOR pathways.

01 Dec 2024·Biochemical Pharmacology

MNAM enhances Blautia abundance and modulates Th17/Treg balance to alleviate diabetes in T2DM mice

Article

Author: Li, Ling ; Li, Ping ; Liu, Ruiqi ; Zhang, Jingfan ; Chen, Yu

This study investigated the therapeutic effects of N¹-Methylnicotinamide (MNAM), a metabolic derivative, on T2DM mice induced by a high-fat diet and streptozotocin (STZ), focusing on its impact on the gut microbiome and immune modulation. MNAM significantly reduced hyperglycemia and enhanced insulin secretion, effects that were dependent on the presence of gut microbiota. It also mitigated STZ-induced weight loss and improved islet cell morphology, reducing islet cell mortality and increasing insulin (INS) levels. Flow cytometry analysis showed a decrease in T helper 17 cells (Th17) and an increase in Treg cells after MNAM treatment, corresponding to the upregulation of Treg markers [interleukin (IL)-10, forkhead box P3 (FOXP3)] and downregulation of Th17 markers [IL17A, RAR-related orphan receptor gamma (RORγt)]. Additionally, MNAM raised anti-inflammatory IL-10 levels while reducing pro-inflammatory cytokines [IL-17α, tumor necrosis factor (TNF-α), IL-6]. Microbiome analysis revealed decreased diversity and increased Blautia abundance post-MNAM administration. Treatment with Blautia not only reversed diabetes indicators but also modulated the Th17/Treg balance and reduced inflammation, with its metabolite sodium acetate mimicking these effects through the G protein-coupled receptor 43 (GPR43) pathway. These findings suggest that MNAM's mitigation of diabetes operates through modulation of the gut microbiota and immune regulation, highlighting Blautia and its metabolite as potential therapeutic agents and providing a theoretical foundation for novel treatment strategies in T2DM.

01 Apr 2024·Structure

Structural characterization of the DNA binding mechanism of retinoic acid-related orphan receptor gamma

Article

Author: Jiang, Longying ; Chen, Zhuchu ; Wei, Hudie ; Liu, Xueke ; Chen, Yongheng ; Dai, Shuyan ; Xiao, Desheng ; Liang, Xujun ; Guo, Ming

Retinoic acid-related orphan receptor gamma (RORγ) plays critical roles in regulating various biological processes and has been linked to immunodeficiency disorders and cancers. DNA recognition is essential for RORγ to exert its functions. However, the underlying mechanism of the DNA binding by RORγ remains unclear. In this study, we present the crystal structure of the complex of RORγ1 DNA-binding domain (RORγ1-DBD)/direct repeat DNA element DR2 at 2.3 Å resolution. We demonstrate that RORγ1-DBD binds the DR2 motif as a homodimer, with the C-terminal extension (CTE) region of RORγ1-DBD contributing to the DNA recognition and the formation of dimeric interface. Further studies reveal that REV-ERB-DBD and RXR-DBD, also bind the DR2 site as a homodimer, while NR4A2-DBD binds DR2 as a monomer. Our research uncovers a binding mechanism of RORγ1 to the DR2 site and provides insights into the biological functions of RORγ1 and the broader RORs subfamily.

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RORγ1

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