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福島県立医科大学学術成果リポジトリ = Fukushima Medical University Repository >
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a10 学術雑誌論文等 = Journal Article >
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http://ir.fmu.ac.jp/dspace/handle/123456789/1061
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| Title: | Prenylated Quinolinecarboxylic Acid Derivative Prevents Neuronal Cell Death Through Inhibition of MKK4 |
| Authors: | Ogura, Masato
Kikuchi, Haruhisa
Shakespear, Norshalena
Suzuki, Toshiyuki
Yamaki, Junko
Homma, Miwako K
Oshima, Yoshiteru
Homma, Yoshimi |
| Affiliation: | 生体物質研究部門
放射性同位元素研究施設 |
| Source title: | Biochemical pharmacology |
| Volume: | 162 |
| Start page: | 109 |
| End page: | 122 |
| Issue Date: | Apr-2019 |
| Abstract: | The development of neuroprotective agents is necessary for the treatment of neurodegenerative diseases. Here, we report PQA-11, a prenylated quinolinecarboxylic acid (PQA) derivative, as a potent neuroprotectant. PQA-11 inhibits glutamate-induced cell death and caspase-3 activation in hippocampal cultures, as well as inhibits N-Methyl-4-phenylpyridinium iodide- and amyloid β1-42-induced cell death in SH-SY5Y cells. PQA-11 also suppresses mitogen-activated protein kinase kinase 4 (MKK4) and c-jun N-terminal kinase (JNK) signaling activated by these neurotoxins. Quartz crystal microbalance analysis and in vitro kinase assay reveal that PQA-11 interacts with MKK4, and inhibits its sphingosine-induced activation. The administration of PQA-11 by intraperitoneal injection alleviates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced degeneration of nigrostriatal dopaminergic neurons in mice. These results suggest that PQA-11 is a unique MKK4 inhibitor with potent neuroprotective effects in vitro and in vivo. PQA-11 may be a valuable lead for the development of novel neuroprotectants. |
| Publisher: | Elsevier |
| language: | eng |
| URI: | http://ir.fmu.ac.jp/dspace/handle/123456789/1061 |
| Full text URL: | http://ir.fmu.ac.jp/dspace/bitstream/123456789/1061/1/BiochemPharmacol_162_p109.pdf |
| ISSN: | 0006-2952
1873-2968 |
| DOI: | 10.1016/j.bcp.2018.10.008 |
| PubMed ID: | 30316820 |
| Other version: | https://doi.org/10.1016/j.bcp.2018.10.008 |
| Rights: | © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. |
| Rights: | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Appears in Collections: | a10 学術雑誌論文等 = Journal Article
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