Targeting lipid clearance pathways to promote repair after SCI

项目总结/摘要 脊髓损伤（SCI）后，损伤部位充满了细胞碎片，特别是髓磷脂碎片， 非常独特的高脂环境巨噬细胞是主要的吞噬细胞， 清理碎片是一项重要的工作，但这一进程不仅效率低下，而且适应不良。髓磷脂的过量 存在于损伤部位的碎片导致形成充满脂质的巨噬细胞（也称为，泡沫状巨噬细胞）， 变得促炎并导致组织再生失败。除了巨噬细胞， 成纤维细胞也变成泡沫细胞。因此，了解髓鞘碎片摄取的机制， 脊髓损伤后的catalysts可能导致新的治疗靶点，以促进脊髓损伤后的修复。在本申请中，我们 将研究髓鞘碎片吸收的机制以及其分解代谢副产物的输出， 巨噬细胞、小胶质细胞和成纤维细胞。此外，我们将测试新的治疗潜力， 纳米颗粒，可以针对吸收和流出机制。

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.