PARP9和PARP14参与阿尔茨海默病中小胶质细胞介导的神经炎性反应  

PARP9 and PARP14 are involved in microglia-mediated neuroinflammation in Alzheimer′s disease

作　　者：黄廉 韦晖 HUANG Lian;WEI Hui(State Key Laboratory of Common Mechanism Research for Major Diseases,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005,China)

机构地区：[1]中国医学科学院基础医学研究所,北京协和医学院基础学院,重大疾病共性机制研究全国重点实验室,北京100005

出　　处：《基础医学与临床》2025年第5期583-588,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金重大项目(32293213)。

摘　　要：目的探究阿尔茨海默病(AD)中免疫细胞激活影响中枢神经系统炎性反应的机制。方法使用人脑单细胞公共数据库GSE161045进行分析,随后使用5×FAD小鼠进行bulk-RNA seq,并在5×FAD小鼠脑石蜡切片中使用免疫荧光染色验证。在小胶质细胞系HMC3中使用Aβ蛋白寡聚体(AβOs)诱导激活并使用Western blot验证PARP9和PARP14蛋白表达水平,最后检测了PARP9和PARP14与免疫浸润之间的关系。结果在AD人脑免疫细胞特别是M2型小胶质细胞中,PARP9和PARP14表达显著上调(P<0.0001),这一结果在5×FAD测序数据中得到了验证,在5×FAD小鼠脑切片中进行免疫荧光染色结果显示Aβ斑块周围的小胶质细胞中PARP9和PARP14的蛋白表达上调,并且在小胶质细胞系HMC3中使用AβOs诱导激活后,PARP9和PARP14的蛋白表达也出现了上调(P<0.05)。结论在AD患者和5×FAD小鼠小胶质细胞中PARP14和PARP9的表达明显增多,且PARP9和PARP14阳性的小胶质细胞显著聚集在Aβ斑块周围,表明PARP9和PARP14可能参与了小胶质细胞对Aβ斑块的免疫调节,促进AD的神经炎性反应。Objective To find specific mechanisms through which immune cell activation affects central nervous system inflammation in Alzheimer′s disease(Alzheimer′s disease,AD).Methods The public single-cell human brain database GSE161045 was applied for analysis.Then bulk RNA sequencing was performed in 5×FAD mice,and the results were validated using immunofluorescence staining microscopy with brain paraffin sections from 5×FAD mice.In the BV2 microglial cell line,AβOs were used to inducing activation and assessed the protein expression of PARP9 and PARP14 with Western blot.Finally,the relationship between PARP9 and PARP14 expression and immune infiltration was examined.Results In AD case,the expression of PARP9 and PARP14 was significantly up regulated(P<0.0001)in human brain immune cells,particularly in M2-type microglia.This result was confirmed by sequencing data from 5×FAD mice.Immunofluorescence staining of brain sections from 5×FAD mice showed up regulated expression of PARP9 and PARP14 in microglia surrounding Aβplaques.Furthermore,in HMC3 cell line,activation induced by AβOs led to a significant increase in the protein expression of PARP9 and PARP14(P<0.05).Conclusions The expression of PARP14 and PARP9 in microglia of AD patients and 5×FAD mice is significantly increased,and PARP9 and PARP14 positive microglia are significantly aggregated around Aβplaques,indicating that PARP9 and PARP14 are potentially involved in the immune regulation of microglia on Aβplaques and promote neuroinflammation in AD.

关 键 词：阿尔茨海默病 PARP9 PARP14 小胶质细胞 神经炎性反应 

分 类 号：R34[医药卫生—基础医学]