JAK2/STAT3 Pathway Inhibition by AG490 Ameliorates Experimental Autoimmune Encephalomyelitis via Regulation of Th17 Cells and Autophagy.

Autor: Xue Y; Department of Neurology, Shijiazhuang People's Hospital, Shijiazhuang, China., Zhang L; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China., Chu L; Department of Neurology, Shijiazhuang People's Hospital, Shijiazhuang, China., Song Z; Department of Neurology, Shijiazhuang People's Hospital, Shijiazhuang, China., Zhang B; Department of Neurology, Shijiazhuang People's Hospital, Shijiazhuang, China., Su X; Department of Neurology, Shijiazhuang People's Hospital, Shijiazhuang, China., Liu W; Department of Neurology, The Third Hospital of Hebei Medical University, Shijiazhuang, China., Li X; Department of Pharmacy, Shijiazhuang People's Hospital, Shijiazhuang, China. Electronic address: 963685787@qq.com.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2024 Aug 06; Vol. 552, pp. 65-75. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1016/j.neuroscience.2024.06.009
Abstrakt: Multiple sclerosis (MS) is an autoimmune inflammatory condition affecting the central nervous system, and experimental autoimmune encephalomyelitis (EAE) animal models have been extensively used to study it. T-helper 17 cells, which produce interleukin-17(IL-17), play crucial roles in MS pathogenesis, and the JAK2/STAT3 pathway has an essential function in their differentiation from naive CD4 + T cells. This study investigated the effects of the JAK2/STAT3 pathway inhibitor AG490 on EAE in vivo and in vitro, as well as the underlying mechanisms. AG490 ameliorated EAE severity and attenuated its typical symptoms by downregulating proteins associated with the JAK2/STAT3 pathway. Furthermore, it decreased T-helper 17 cell differentiation from naive CD4 + T cells by inactivating STAT3. In addition, it conferred protective effects against EAE by restoring autophagy. These findings indicate the potential of AG490 as a candidate anti-MS therapeutic.
(Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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