Nrf2 signaling pathway: Pivotal roles in inflammation.

The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state.

Nrf2 as regulator of innate immunity: A molecular Swiss army knife!

Inosine monophosphate dehydrogenase (IMPDH) of human is an attractive target for immunosuppressive agents. Currently, small-molecule inhibitors do not show good selectivity for different IMPDH isoforms (IMPDH1 and IMPDH2), resulting in some adverse effects, which limit their use. Herein, we used a small-molecule probe specifically targeting IMPDH2 and identified Cysteine residue 140 (Cys140) as a selective druggable site. On covalently binding to Cys140, the probe exerts an allosteric regulation to block the catalytic pocket of IMPDH2 and further induces IMPDH2 inactivation, leading to an effective suppression of neuroinflammatory responses. However, the probe does not covalently bind to IMPDH1. Taken together, our study shows Cys140 as a druggable site for selectively inhibiting IMPDH2, which provides great potential for development of therapy agents for autoimmune and neuroinflammatory diseases with less unfavorable tolerability profile.

https://www.pnas.org/content/pnas/114/29/E5986.full.pdf

Highly selective inhibition of IMPDH2 provides the basis of antineuroinflammation therapy.

Spinal cord injury (SCI) is a significant cause of disability, and treatment alternatives that generate beneficial outcomes and have no side effects are urgently needed. SCI may be treatable if intervention is initiated promptly. Therefore, several treatment proposals are currently being evaluated. Inflammation is part of a complex physiological response to injury or harmful stimuli induced by mechanical, chemical, or immunological agents. Neuroinflammation is one of the principal secondary changes following SCI and plays a crucial role in modulating the pathological progression of acute and chronic SCI. This review describes the main inflammatory events occurring after SCI and discusses recently proposed potential treatments and therapeutic agents that regulate inflammation after insult in animal models.

/pdf/inflammation-a-target-for-treatment-in-spinal-cord-injury-la01x83y.pdf

Inflammation: A Target for Treatment in Spinal Cord Injury

Sappanone A exhibits anti-inflammatory effects via modulation of Nrf2 and NF-κB.

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Sappanone A exhibits anti-inflammatory effects via modulation of Nrf2 and NF-κB.