A Docosahexaenoic Acid-Derived Pro-resolving Agent, Maresin 1, Protects Motor Neuron Cells Death
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Maresin 1 is a novel pro-resolving mediator derived from docosahexaenoic acid (DHA), with potent anti-inflammation effects against several animal models, including brain ischemia, sepsis, and lung fibrosis. However, its effect against motor neuron cell death is still not investigated. Therefore, we investigated the effects of maresin 1 on several stress-induced motor neuron cell death. Maresin 1 suppressed combinatorial stress which was evoked by superoxide dismutase 1 (SOD1)G93A and serum-free, -induced motor neuron cells death in a concentration-dependent manner, and had a stronger neuroprotective effective than DHA. Maresin 1 also had neuroprotective effects against transactivation response DNA-binding protein (TDP)-43A315T and serum-free stress, H2O2, and tunicamycin-induced cell death. Maresin 1 reduced the reactive oxygen species (ROS) production caused by SOD1G93A or TDP-43A315T. Moreover, maresin 1 suppressed the NF-κB activation induced by SOD1G93A and serum-free stress. These data indicate that maresin 1 has motor neuron protective effects against several stresses by reduction of ROS production or attenuation of the NF-κB activation. Maresin 1 also had neuroprotective effects against H2O2, and tunicamycin-induced cell death in a concentration-dependent manner. Finally, maresin 1 ameliorated the motor function deficits of spinal muscular atrophy model in which endoplasmic reticulum stress was upregulated. Thus, maresin 1 may be beneficial to protect against motor neuron diseases.
KeywordsMaresin 1 Amyotrophic lateral sclerosis Spinal muscular atrophy Reactive oxygen species Nuclear factor-kappa B
YO, MJ, KO: study design, the collection, analysis and interpretation of data, the writing of the report; KT: study design, the collection, analysis and interpretation of data; SO, SY: study design and the decision to submit the article for publication; HH, MS: study design, the collection, analysis and interpretation of data, the writing of the report and the decision to submit the article for publication.
This work was supported by Ono pharmaceutical Co., Ltd (Osaka, Japan) in this manuscript. This sponsor is involved in the study design and the decision to submit the article for publication.
Compliance with Ethical Standards
Conflict of interest
Prof. Hideaki Hara has received a research grant from Ono pharmaceutical Co., Ltd. The other authors declare that have no conflict of interest.
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