Targeting Lipid Clearance Pathways to Promote Repair After SCI

项目摘要/摘要 脊髓损伤(SCI)后，损伤部位充满了细胞碎片，特别是髓鞘碎片，产生了 非常独特的脂类致密环境。巨噬细胞是主要的吞噬细胞，负责 这一进程不仅效率低下，而且适应性差。过量的髓鞘 损伤部位存在的碎片导致形成富含脂质的巨噬细胞(又名。泡沫巨噬细胞) 变得容易发炎，并导致组织再生失败。除了巨噬细胞，小胶质细胞 成纤维细胞也会变成泡沫细胞。因此，了解髓鞘碎片摄取和 脊髓损伤后的分解代谢可能导致新的治疗靶点来促进脊髓损伤后的修复。在此应用程序中，我们 将研究髓鞘碎片摄取的机制以及其分解代谢副产物在 脊髓损伤后巨噬细胞、小胶质细胞和成纤维细胞。此外，我们还将测试新药的治疗潜力 可以靶向摄取和排出机制的纳米颗粒。

PROJECT SUMMARY/ABSTRACT After spinal cord injury (SCI), the injury site is filled with cellular debris, especially myelin debris that creates a very unique lipid-dense environment. Macrophages are the predominant phagocyte that are responsible for debris-clearance, but this process is not only inefficient, it is also maladaptive. The excessive amount of myelin debris present at the injury site leads to formation lipid-laden macrophages (a.k.a. foamy macrophages) that become pro-inflammatory and contribute to tissue regeneration failure. In addition to macrophages, microglia and fibroblasts also become foam cells. Therefore, understanding the mechanisms of myelin debris uptake and catabolism after SCI may lead to novel therapeutic targets to promote repair after SCI. In this application, we will investigate the mechanism of myelin debris uptake as well as the export of its catabolic byproduct in macrophages, microglia, and fibroblasts after SCI. In addition, we will test the therapeutic potential of novel nanoparticles that can target the uptake and efflux mechanisms.