ASK1 activation in glial cells in post-mortem multiple sclerosis tissue.

IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY
Neuropathology Pub Date : 2024-05-22 DOI:10.1111/neup.12978
Erika Seki, Xiaoli Guo, Kazuhiko Namekata, Takashi Komori, Hiroyuki Hayashi, Nobutaka Arai, Takayuki Harada
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引用次数: 0

Abstract

Multiple sclerosis (MS), the leading cause of disability in young adults, is an inflammatory disease of the central nervous system characterized by localized areas of demyelination. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been shown to be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Interestingly, ASK1 signaling regulates glial cell interactions and drives neuroinflammation in EAE mice. To further investigate its clinical significance, in the present study, we examined the activation of ASK1 in the post-mortem brain of MS patients. ASK1 activation was found in active lesions of the corpus callosum in both microglia/macrophages and astrocytes. Moreover, ASK1 activation in astrocytes was higher than that in microglia/macrophages, which was in line with our findings in EAE mice. Our results suggest an important role of ASK1 in glial cells, indicating that ASK1 might be a good therapeutic target for MS.

多发性硬化症死后组织神经胶质细胞中的 ASK1 激活。
多发性硬化症(MS)是青壮年致残的主要原因,是一种以局部脱髓鞘区域为特征的中枢神经系统炎症性疾病。凋亡信号调节激酶1(ASK1)是一种丝裂原活化蛋白激酶,已被证明与多发性硬化症小鼠模型--实验性自身免疫性脑脊髓炎(EAE)的发病机制有关。有趣的是,ASK1 信号调节神经胶质细胞的相互作用,并驱动 EAE 小鼠的神经炎症。为了进一步研究其临床意义,我们在本研究中检测了多发性硬化症患者死后大脑中 ASK1 的激活情况。在胼胝体活动性病变中的小胶质细胞/巨噬细胞和星形胶质细胞中都发现了 ASK1 的活化。此外,星形胶质细胞中的ASK1活化高于小胶质细胞/巨噬细胞,这与我们在EAE小鼠中的发现一致。我们的研究结果表明,ASK1在神经胶质细胞中起着重要作用,这表明ASK1可能是多发性硬化症的一个很好的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neuropathology
Neuropathology 医学-病理学
CiteScore
4.10
自引率
4.30%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
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