MFG-E8 抑制 Aβ诱导的小胶质细胞产生抗菌肽 cathelicidin：阿尔茨海默病的合适靶点。
MFG-E8 inhibits Aβ-induced microglial production of cathelicidin-related antimicrobial peptide: A suitable target against Alzheimer's disease.
机构信息
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.
出版信息
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。
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