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 |
DOI | 10.1016/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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