Song, Gyun Jee Rahman, Md Habibur Jha, Mithilesh Kumar Gupta, Deepak Prasad Park, Sung Hee Kim, Jae-Hong Lee, Sun-Hwa Lee, In-Kyu Sim, Taebo Bae, Yong Chul Lee, Won-Ha Suk, Kyoungho 2024-01-19T20:03:12Z 2024-01-19T20:03:12Z 2022-01-25 2019-05 1663-9812 https://pubs.kist.re.kr/handle/201004/120020 GNF-2 is an allosteric inhibitor of Bcr-Abl. It was developed as a new class of anti-cancer drug to treat resistant chronic myelogenous leukemia. Recent studies suggest that c-Abl inhibition would provide a neuroprotective effect in animal models of Parkinson's disease as well as in clinical trials. However, the role of c-Abl and effects of GNF-2 in glia-mediated neuroinflammation or pain hypersensitivity has not been investigated. Thus, in the present study, we tested the hypothesis that c-Abl inhibition by GNF-2 may attenuate the inflammatory activation of glia and the ensuing pain behaviors in animal models. Our results show that GNF-2 reduced lipopolysaccharide (LPS)-induced nitric oxide and pro-inflammatory cytokine production in cultured glial cells in a c-Abldependent manner. The small interfering ribonucleic acid (siRNA)-mediated knockdown of c-Abl attenuated LPS-induced nuclear factor kappa light chain enhancer of activated B cell (NE-kappa B) activation and the production of pro-inflammatory mediators in glial cell cultures. Moreover, GNF-2 administration significantly attenuated mechanical and thermal hypersensitivities in experimental models of diabetic and inflammatory pain. Together, our findings suggest the involvement of c-Abl in neuroinflammation and pain pathogenesis and that GNF-2 can be used for the management of chronic pain. English FRONTIERS MEDIA SA A Bcr-Abl Inhibitor GNF-2 Attenuates Inflammatory Activation of Glia and Chronic Pain Article 10.3389/fphar.2019.00543 1 FRONTIERS IN PHARMACOLOGY, v.10 FRONTIERS IN PHARMACOLOGY 10 N scie scopus 000468408000001 2-s2.0-85068846628 Pharmacology & Pharmacy Pharmacology & Pharmacy Article C-ABL OXIDATIVE STRESS TYROSINE KINASE MICROGLIAL ACTIVATION PARKINSONS-DISEASE PIVOTAL ROLE NEUROINFLAMMATION PHOSPHORYLATION SYNUCLEIN PATHOGENESIS GNF-2 c-Abl glia neuroinflammation pain