Structure-activity relationship (SAR) studies of N-(3-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (SRI-22819) as NF-ҡB activators for the treatment of ALS

Mathew, Biji; Ruiz, Pedro; Dutta, Shilpa; Entrekin, Jordan T.; Zhang, Sixue; Patel, K.D.; Simmons, Micah; Augelli‐Szafran, Corinne E.; Cowell, Rita M.; Suto, Mark J.

doi:10.1016/j.ejmech.2020.112952

Cited by 4 publications

(3 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the second part of the experiment, all rats were randomly assigned to four groups: TBI group, LPS group (TBI +LPS), TLR-4 group, and NF-κB group. The TRL4 inhibitor (TAK-3, MedChemExpress, China) 28 and NFkB agonist (NFkB activator-2 MCE, China) 31 were utilized. Each group was further divided into two subgroups; one subgroup (n=3) was designated for fluorescence staining while the other subgroup (n=3) was allocated for Western blot assay and enzyme-linked immunosorbent assay (ELISA).…”

Section: Dovepressmentioning

confidence: 99%

“…18,22,25 NF-κB is intricately linked to the expression of a diverse array of cytokines and plays a pivotal role in mediating inflammatory responses, oxidative stress, apoptosis, and other pathological processes. 31,37 The NF-κB family comprises five interconnected subunits, namely P50, P52, P65, RelB, and c-Rel. Previous research has indicated that the activation of the immune system occurs through TLR-4 binding to LPS.…”

mentioning

confidence: 99%

“…28,30,40 To further investigate the role of the TLR-4/ NF-κB pathway in mediating secondary TBI, we employed NF-κΒ activator 2 to augment the expression and activation of NF-κB. 31 The findings demonstrated that the upregulation and activation of NF-κB led to an elevation in inflammatory cytokines and recruitment of inflammatory cells within the brain. After treatment with NF-κΒ activator 2, we observed However, this study also has certain limitations.…”

mentioning

confidence: 99%

See 2 more Smart Citations

TAK-3 Inhibits Lipopolysaccharide-Induced Neuroinflammation in Traumatic Brain Injury Rats Through the TLR-4/NF-κB Pathway

Hou,

Yang,

et al. 2024

JIR

View full text Add to dashboard Cite

The activation of the inflammatory response is regarded as a pivotal factor in the pathogenesis of TBI. Central nervous system infection often leads to the exacerbation of neuroinflammation following TBI, primarily caused by Gram-negative bacteria. This study aims to elucidate the effects of the novel anti-inflammatory drug TAK-3 on LPS-induced neuroinflammation in TBI rats. Methods: In conjunction with the rat controlled cortical impact model, we administered local injections of Lipopolysaccharide to the impact site. Subsequently, interventions were implemented through intraperitoneal injections of TAK-3 and NF-κB activitor2 to modulate the TLR4/NF-κB axis The impact of LPS on neurological function was assessed using mNSS, open field test, and brain water content measurement. Inflammatory markers, including TNF-α, IL-1β, IL-6 and IL-10 were assessed to evaluate the condition of neuritis by Elisa. The activation of the TLR-4/NF-κB signaling pathway was detected by immunofluorescence staining and Western blot to assess the anti-inflammatory effects of TAK-3. Results: The administration of LPS exacerbated neurological damage in rats with TBI, as evidenced by a reduction in motor activity and an increase in anxiety-like behavior. Furthermore, LPS induced disruption of the blood-brain barrier integrity and facilitated the development of brain edema. The activation of microglia and astrocytes by LPS at the cellular and molecular levels has been demonstrated to induce a significant upregulation of neuroinflammatory factors. The injection of TAK-3 attenuated the neuroinflammatory response induced by LPS. Conclusion:The present study highlights the exacerbating effects of LPS on neuroinflammation in TBI through activation of the TLR-4/NF-κB signaling pathway. TAK-3 can modulate the activity of this signaling axis, thereby attenuating neuroinflammation and ultimately reducing brain tissue damage.

show abstract

Section: Dovepressmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation