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bioRxiv · 10.1101/2025.09.02.673863

DRP1 induces neuroinflammation via transcriptional regulation of NF-ĸB

Lai, Y.·Fan, R. Z.·Brown, H. J.·Salehe, S. S.·Tieu, E. K.·Tieu, K.
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Abstract

Neuroinflammation is a major pathogenic mechanism in neurodegenerative diseases. Understanding the regulation of neuroinflammation is critical to therapeutic development. We report here that dynamin related protein 1 (DRP1), well-recognized for its role in mitochondrial fission, is a transcription factor that regulates neuroinflammation. Using multiple inflammatory models, we provide evidence demonstrating that DRP1, when challenged with pro-inflammatory lipopolysaccharides, translocates from the cytosol to the nucleus, then binds to the promoter region of Rela (encoding NF-{kappa}B) to activate its gene products and other downstream inflammatory cytokines. Our data also demonstrate the significant role of the proinflammatory lipocalin 2 in the brain. In combination, this study highlights a previously unidentified function of DRP1 in mediating neuroinflammation via the NF-{kappa}B-lipocalin 2 axis. Through such mechanisms of DRP1, this study also provides potential therapeutic targets for neurodegenerative diseases and other conditions linked to inflammation.

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Lai, Y., Fan, R. Z., Brown, H. J., Salehe, S. S., Tieu, E. K., Tieu, K.. 2025-09-06. DRP1 induces neuroinflammation via transcriptional regulation of NF-ĸB. https://doi.org/10.1101/2025.09.02.673863

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