| First Author | Favret J | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 31822 |
| PubMed ID | 39738378 | Mgi Jnum | J:361372 |
| Mgi Id | MGI:7798402 | Doi | 10.1038/s41598-024-82927-1 |
| Citation | Favret J, et al. (2024) Ablation of lipocalin-2 reduces neuroinflammation in a mouse model of Krabbe disease. Sci Rep 14(1):31822 |
| abstractText | Lipocalin-2 (LCN2) is an acute-phase secretory molecule significantly upregulated in various neuroinflammatory and demyelinating conditions. Krabbe disease (KD) is a neurodegenerative lysosomal disorder caused by a galactosylceramidase (GALC) deficiency, accumulating cytotoxic psychosine in nervous systems, and subsequent neuroinflammation. Here, we show that LCN2 is highly overexpressed in GALC-deficient astrocytes. To further understand if the elevated LCN2 is critical for KD progression, we globally deleted Lcn2 in the Galc-knockout (KO) mouse model. Interestingly, the Galc and Lcn2 double KO mice showed dramatically reduced neuroinflammation including gliosis. Pro-inflammatory cytokines such as TNF-alpha, MMP3, and MCP-1 were significantly downregulated in the brain of the double KO mice compared to Galc-KO. In addition, the ablation of Lcn2 marginally increased the survival and attenuated disease progression in Galc-KO mice. However, the accumulation of psychosine was not altered in the brain by LCN2 deficiency. Our findings suggest that the upregulation of LCN2 is crucial for the aggravation of neuroinflammation in a mouse model of Krabbe disease. |
