中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid

Tyrphostin A9 protects axons in experimental autoimmune encephalomyelitis through activation of ERKs

文献类型:期刊论文

作者Dai, Xiaodong3,4; Wang, Yongmei3,4; Li, Yuexin1,5; Zhong, Yongping5; Pei, Min3,4; Long, Jing3,4; Dong, Xingchen3,4; Chen, Yi-Li3,4; Wang, Qi3,4; Wang, Guifeng3,4
刊名LIFE SCIENCES
出版日期2022-04-01
卷号294页码:12
ISSN号0024-3205
关键词Multiple sclerosis (MS) Experimental autoimmune encephalomyelitis (EAE) Extracellular signal-regulated kinase Tyrphostin A9
DOI10.1016/j.lfs.2022.120383
通讯作者Wang, Chunhe(wangc@simm.ac.cn)
英文摘要Aims: Small molecule compound tyrphostin A9 (A9), an inhibitor of platelet-derived growth factor (PDGF) receptor, was previously reported by our group to stimulate extracellular signal-regulated kinase 1 (ERK1) and 2 (ERK2) in neuronal cells in a PDGF receptor-irrelevant manner. The study aimed to investigate whether A9 could protect axons in experimental autoimmune encephalomyelitis through activation of ERKs.& nbsp;Main methods: A9 treatment on the protection on neurite outgrowth in SH-SY5Y neuroblastoma cells and primary substantia nigra neuron cultures from the neurotoxin MPP+ were analyzed. Then, clinical symptoms as well as ERK1/2 activation, axonal protection induction, and the abundance increases of the regeneration biomarker GAP-43 in the CNS in the relapsing-remitting experimental autoimmune encephalomyelitis (EAE) model were verified.& nbsp;Key findings: A9 treatment could stimulate neurite outgrowth in SH-SY5Y neuroblastoma cells and protect primary substantia nigra neuron cultures from the neurotoxin MPP+. In the relapsing-remitting EAE model, oral administration of A9 successfully ameliorated clinical symptoms, activated ERK1/2, induced axonal protection, and increased the abundance of the regeneration biomarker GAP-43 in the CNS. Interestingly, gene deficiency of ERK1 or ERK2 disrupted the beneficial effects of A9 in MOG-35-55-induced EAE.& nbsp;Significance: These results demonstrated that small molecule compounds that stimulate persistent ERK activation in vitro and in vivo may be useful in protective or restorative treatment for neurodegenerative diseases.
WOS关键词SIGNAL-REGULATED KINASE ; NERVE GROWTH-FACTOR ; PHEOCHROMOCYTOMA CELLS ; MULTIPLE-SCLEROSIS ; FK506 ; NEUROPROTECTION ; STIMULATION ; INDUCTION ; CASCADE ; MODEL
资助项目Department of Veterans Affairs Biomedical Laboratory Research and Development of the United States of America[BX000810] ; NIH Grant (United States of America)[MH045372] ; National Multiple Sclerosis So-ciety Research Grants (United States of America) ; Collins Medical Foundation (Portand, Oregon, United States of America) ; Na-tional Natural Science Foundation of PR China (China)[81872785]
WOS研究方向Research & Experimental Medicine ; Pharmacology & Pharmacy
语种英语
出版者PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号WOS:000777804900002
源URL[http://119.78.100.183/handle/2S10ELR8/299538]  
专题中国科学院上海药物研究所
通讯作者Wang, Chunhe
作者单位1.VA Portland Hlth Care Syst, Res Serv, Portland, OR 97239 USA
2.Oregon Hlth & Sci Univ, Anesthesiol & Perioperat Med, Portland, OR 97239 USA
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200126, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA
6.Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA
7.Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA
推荐引用方式
GB/T 7714
Dai, Xiaodong,Wang, Yongmei,Li, Yuexin,et al.

Tyrphostin A9 protects axons in experimental autoimmune encephalomyelitis through activation of ERKs

[J]. LIFE SCIENCES,2022,294:12.
APA Dai, Xiaodong.,Wang, Yongmei.,Li, Yuexin.,Zhong, Yongping.,Pei, Min.,...&Wang, Chunhe.(2022).

Tyrphostin A9 protects axons in experimental autoimmune encephalomyelitis through activation of ERKs

.LIFE SCIENCES,294,12.
MLA Dai, Xiaodong,et al."

Tyrphostin A9 protects axons in experimental autoimmune encephalomyelitis through activation of ERKs

".LIFE SCIENCES 294(2022):12.

入库方式: OAI收割

来源:上海药物研究所

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