Fig. 8: Conceptual framework illustrating how DRP1 induces neuroinflammation via the NF-κB–lipocalin-2 axis.
From: DRP1 induces neuroinflammation via transcriptional regulation of NF-ĸB.
Upon stimulation with proinflammatory signals such as LPS through TLR4, DRP1 translocates from the cytosol into the nucleus, where it binds to the Rela promoter and enhances its transcription. Increased NF-κB p65 subsequently drives the expression of downstream inflammatory cytokines that can ultimately contribute to neurotoxicity. Microglia express higher basal levels of TLR4 than astrocytes and therefore respond earlier and more robustly to LPS. In contrast, astrocytic activation requires “priming” by cytokines released from activated microglia72,73,74, making microglia the predominant initiators of the inflammatory cascade. Among NF-κB–regulated genes, Lcn2 (encoding lipocalin-2) is the most inducible in a cell-type-dependent manner. Once secreted, lipocalin-2 further amplifies neuroinflammation in neighboring cells. This graph was created in BioRender. Lai, Y. (2026) https://BioRender.com/meryu9q.
