Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Autism spectrum disorders (ASD) are neurodevelopmental disorders that are characterized by repetitive behaviors, and impairments in communication and social interaction. Studies have shown that activation of peroxisome proliferator-activated receptor-delta (PPARδ) causes anti-inflammatory effects in animal models of neuroinflammatory diseases. We investigated the possible anti-inflammatory effect of a PPARδ agonist, GW0742 in the BTBR T Itpr3tf/J (BTBR) mouse model of autism. BTBR and C57BL/6 (B6) mice were treated orally with GW0742 (30 mg/kg, p.o., once daily) for 7 days. Effect of GW0742 treatment on repetitive behavior, marble burying, and thermal sensitivity response was assessed on day 8. We further examined the effect of GW0742 treatment on immunological parameters in splenocytes using flow cytometry (CD4TIM-3, IL-17ATIM-3, IL-17ACD4, RORγTTIM-3, RORγTCD4, Stat3TIM-3, Foxp3TIM-3, Foxp3CD4, and IFN-γCD4). We also explored the effects of GW0742 on mRNA and protein expression of TIM-3, IL-17A, RORγT, Stat3, IFN-γ, Foxp3, and IL-10 in the brain tissue using RT-PCR and western blot analyses. GW0742 treatment substantially decreased repetitive behaviors, and lowered thermal sensitivity response in BTBR mice. GW0742 attenuated the expression of inflammatory markers such as IL-17A, RORγT, Stat3, TIM-3, and IFN-γ, while upregulating anti-inflammatory markers such as IL-10/Foxp3 both in the brain and periphery of BTBR mice. In conclusion, this study suggests that GW0742 corrects neurobehavioral dysfunction in BTBR mice which is concurrent with modulation of multiple signaling pathways.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neuint.2018.09.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The PPAR-β/δ agonist GW0742 alleviates DNA damage and lupus nephritis in an animal model of systemic lupus erythematosus via restoring DNA repair gene expression.
Mutat Res Genet Toxicol Environ Mutagen
August 2025
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address:
Systemic lupus erythematosus (SLE) is a persistent autoimmune inflammatory disease associated with an elevated risk of kidney damage. The etiology of SLE remains unclear; nevertheless, current investigations increasingly indicate that increased DNA damage and deficiencies in the mechanisms of its repair might contribute to its pathogenesis, necessitating the identification and management of the disease. Therapies for SLE have improved considerably over recent decades.
View Article and Find Full Text PDFRational design and synthesis of 6-(piperazin-1-yl)imidazo[1,2-b]pyridazine derivatives as dual FXR/PPARδ agonists for treatment of pulmonary fibrosis.
Eur J Med Chem
November 2025
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address:
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive multifactorial lung disorder characterized by excessive deposition of fibrotic connective tissue. The activation of farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor δ (PPARδ) demonstrated therapeutic efficacy in reducing fibrotic pathology, respectively, suggesting that dual FXR/PPARδ up-regulators may provide a prospective approach to address the polypharmacy dilemma in fibrotic diseases. Herein, the identification campaign of 6-(piperazin-1-yl)imidazo[1,2-b]pyridazine derivatives as FXR/PPARδ dual agonists was described through hybridation of FXR agonist GW-4064 and PPARδ agonist GW-0742.
View Article and Find Full Text PDFIdentification of MMP14 and MKLN1 as colorectal cancer susceptibility genes and drug-repositioning candidates from a genome-wide association study.
J Transl Med
May 2025
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Korea.
Background: Genome-wide association studies (GWAS) and subsequent functional interpretation have been used to identify susceptible genes and potential drug-repositioning candidates. This study aimed to identify genes associated with colorectal cancer (CRC) and potential drug-repositioning candidates.
Methods: Patients with CRC at Seoul National University Hospital (SNUH, discovery study) and Chonnam National University Hospital (CNUH, replication study) were included as case groups.
PPARγ/β/δ Agonists Can Ameliorate Dextran Sodium Sulfate-Induced Colitis and Modulate Gut Microbiota.
J Gastroenterol Hepatol
June 2025
Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
Background And Aim: Peroxisome proliferator-activated receptors (PPARs), as nuclear receptors, modulate both lipid metabolism and inflammatory/immune processes. This study examines the impact of modulating the activities of the PPAR subtypes PPARβ/ð and PPARγ on the gut microbiota in inflammatory bowel disease (IBD).
Methods: Mice with dextran sulfate sodium (DSS)-induced acute colitis were treated with the PPARγ agonist pioglitazone, PPARβ/δ agonist GW0742, or their respective antagonists (GW9662, GSK3787).
Phenolic and Iridoid Glycosides from L. and Their Effects on the α, δ, and γ Subtypes of the PPAR System-Including the Discovery of the Novel Phenylethanoid Cardiaphenyloside A and the Most Active 7-Chloro-6-desoxy-harpagide.
Molecules
January 2025
Department of Pharmaceutical Biology, Leipzig University, Johannisallee 21, 04103 Leipzig, Germany.
L. is known in Europe for its cardioactivity-also in interrelation with known risk factors of the metabolic syndrome-just as Houtt. in East Asia; however, up to now, no active constituents could be identified.
View Article and Find Full Text PDF