| First Author | Lai Y | Year | 2026 |
| Journal | Nat Commun | Volume | 17 |
| Issue | 1 | PubMed ID | 41839890 |
| Mgi Jnum | J:384920 | Mgi Id | MGI:8330234 |
| Doi | 10.1038/s41467-026-70780-x | Citation | Lai Y, et al. (2026) DRP1 induces neuroinflammation via transcriptional regulation of NF-kB. Nat Commun 17(1) |
| abstractText | Neuroinflammation is a major pathogenic mechanism underlying neurodegenerative diseases. Understanding how neuroinflammation is regulated is critical to therapeutic development. Here, we report that dynaminrelated protein 1 (DRP1), well-recognized for its role in mitochondrial fission, also functions as a transcription factor that regulates neuroinflammation. Using multiple inflammatory models, we demonstrate that upon stimulation with pro-inflammatory lipopolysaccharides (LPS), DRP1 translocates from the cytosol to the nucleus, where it binds to the promoter region of Rela (encoding NF-kappaB p65) to activate its gene products and other downstream inflammatory cytokines. Our data further reveal a significant role of the proinflammatory lipocalin-2 in the brain. In combination, this study identifies a previously unrecognized function of DRP1 in mediating neuroinflammation via the NF-kappaB-lipocalin-2 axis and highlights DRP1-mediated pathways as potential therapeutic targets for neurodegenerative and other inflammation-related diseases. |
