**5. Conclusions**

To the best of our knowledge, the present data demonstrate, for the first time, the selective neuroprotective e ffects of CDDO-Me against SE. Briefly, CDDO-Me attenuated SE-induced CA1 neuronal death, but not hilus interneurons, by facilitating DRP1-mediated mitochondrial fission via ERK1/2 and JNK activation. Unlike CDDO-Me, LONP1 siRNA did not influence the expression and phosphorylation of DRP1, ERK1/2, JNK and PP2B under physiological- and post-SE conditions. In addition, LONP1 knockdown induced massive degeneration of dentate granule cells, and aggravated loss of CA1 neurons and hilus interneurons following SE. Co-treatment of CDDO-Me with LONP1 siRNA ameliorated CA1 neuronal death concomitant with abrogation of mitochondrial elongation induced by SE. Therefore, we provide an underlying mechanism of CDDO-Me for mitochondrial fission independent of LONP1 activity, and propose the availability of CDDO-Me for various neurological diseases relating to aberrant mitochondrial dynamics.

**Author Contributions:** T.-C.K. designed and supervised the project. J.-E.K., H.P., S.-H.C. and M.-J.K. performed the experiments described in the manuscript. J.-E.K. and T.-C.K. analyzed the data, and wrote the manuscript.

**Funding:** This study was supported by a gran<sup>t</sup> of National Research Foundation of Korea (NRF) gran<sup>t</sup> (No. 2018R1A2A2A05018222). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

**Conflicts of Interest:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
