摘要
高迁移率族蛋白B1(High mobility group box protein-1,HMGB1)和小胶质细胞在阿尔茨海默病(Alzheimer’s disease,AD)疾病的发生发展中起了重要的作用。HMGB1不但参与了其神经炎症的过程,并能抑制小胶质细胞对Aβ清除。通过受体结合激活了NF-κB轴信号通路的级联反应,启动基因转录和表达,释放大量炎症介质和转录产物,加重了AD的炎症反应,但有研究表明不同转录因子有不同作用,如P50敲除具有保护作用,但P65激活也具有保护作用。HMGB1通过紧密结合Aβ42,使Aβ42处于稳定的寡聚体状态,减弱小胶质细胞对Aβ42清除的能力。Aβ可直接与小胶质细胞上TLR结合,尤其是TLR2、TLR4,可以促进小胶质细胞分泌各种细胞因子和趋化因子,正反馈促进小胶质细胞的激活以及对Aβ的清除。HMGB1和小胶质细胞对Aβ清除之间失衡也是AD发生及进展的重要原因之一,因此HMGB1可能成为治疗AD的一种新的靶标。
High mobility group protein B I（HMGB 1 ） and microglia play an important role in Alzheimer＇s disease（AD） development. HMGB1 not only involve in the process of the inflammation of the nerve, and can inhibit the removal of Aβ. With combining the receptor, HMGB1 can activate a cascade of NF-KB signal pathway, promote gene transcrip- tion and expression, release lots of inflammatory mediators and transcription products, aggravate the inflammatory re- action in AD. But some studies have shown that different transcription factors have different effects, such as P50 knocked has a protective effect, but p65 activated also have a protective effect. HMGB1 tight binding of Aβ42 ,which make the Aβ42 in a stable state of the oligomer, weakening the ability of remove the Aβ42 in microglia. Aβ can be directly combined with TLR in microglia, especially TLR4 and TLR2, which can promote the secretion of various cy- tokines and chemokines, and positive feedback to promote the activation of the removal of Aβ in microglia. The imbal- ance between HMGBI and microglia in Aβ clearance is one of the important reasons for the occurrence and progres- sion of AD. Therefore, HMGB 1 may be a novel therapeutic target for the treatment of AD.
出处
《中国现代医生》
2016年第22期164-168,共5页
China Modern Doctor
基金
国家自然科学基金(81271204)
浙江省公益技术应用研究计划项目(2016C37098)
