Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province 510080, People's Republic of China.
Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, People's Republic of China.
Cell Immunol. 2018 Sep;331:59-66. doi: 10.1016/j.cellimm.2018.05.008. Epub 2018 May 24.
Neuroinflammation plays a pivotal role in the incidence and progression of Alzheimer's disease (AD). Cathelicidin-related antimicrobial peptide (CRAMP) is critically involved in the innate neuronal responses of chronic neuroinflammation in AD and thus plays a key role in the disease. Here, we show that Aβ42 induced microglial production of CRAMP, which was effectively inhibited by milk-fat globule-epidermal growth factor 8 (MFG-E8). Production of CRAMP was associated with activation of ERK1/2, p38 and phospho-P65-NF-kB upregulation. Additionally, the phosphorylation of these signaling proteins was also reversed by MFG-E8. Pre-incubation with signaling inhibitors confirmed that MFG-E8 has a regulatory role on CRAMP through MAPK and NF-kB signaling pathways. MFG-E8 treatment may thus be a potential pharmacotherapy for chronic inflammation in AD.
神经炎症在阿尔茨海默病（AD）的发病和进展中起着关键作用。抗菌肽相关 cathelicidin（CRAMP）在 AD 慢性神经炎症的先天神经元反应中起关键作用，因此在疾病中起关键作用。在这里，我们发现 Aβ42 诱导小胶质细胞产生 CRAMP，而 MFG-E8（牛奶脂肪球-表皮生长因子 8）可有效抑制其产生。CRAMP 的产生与 ERK1/2、p38 和磷酸化 P65-NF-kB 上调有关。此外，MFG-E8 还逆转了这些信号蛋白的磷酸化。信号抑制剂的预孵育证实，MFG-E8 通过 MAPK 和 NF-kB 信号通路对 CRAMP 具有调节作用。因此，MFG-E8 治疗可能是 AD 慢性炎症的一种潜在药物治疗方法。
