热休克蛋白70结合蛋白1诱导星形胶质细胞内源性突变亨廷顿蛋白积聚  

Heat Shock Protein 70-binding Protein 1 Induces the Aggregation of Endogenous Mutant Hun⁃tingtin in Astrocytes

作　　者：彭希 覃禹森 严丽[2] 静亮 PENG Xi;QIN Yusen;YAN Li;JING Liang(Department of Nursing,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Depart-ment of Emergency-critical Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院护理部,武汉430030 [2]华中科技大学同济医学院附属同济医院急诊-重症医学科,武汉430030

出　　处：《神经损伤与功能重建》2023年第12期705-708,713,共5页Neural Injury and Functional Reconstruction

基　　金：湖北省自然科学基金项目(No.2023AFB713)。

摘　　要：目的:探讨热休克蛋白70结合蛋白1(heat shock protein 70 binding protein 1,HspBP1)能否促进内源性突变亨廷顿蛋白(mutant Huntingtin,mHTT)在星形胶质细胞中积聚,并确定其是否能够介导病理性损伤。方法:在GFAP-HD转基因小鼠的星形胶质细胞中过表达HspBP1,通过免疫染色和蛋白印迹法检测mHTT和神经病理相关蛋白表达水平,并通过行为学实验观察小鼠的运动功能水平。结果:GFAP-HD转基因小鼠短期内即出现星形胶质细胞中的mHTT积聚以及运动功能障碍,但并未出现星形胶质细胞活化和神经元损伤。结论:HspBP1能够通过促进星形胶质细胞内源性mHTT积聚介导病理性损伤,但mHTT在神经元和星形胶质细胞中共同表达可能是神经元显著变性的必需条件。Objective:To investigate whether heat shock protein 70 binding protein 1(HspBP1)can promote the aggregation of endogenous mutant huntingtin(mHTT)in astrocytes and determine whether it can mediate pathological damage.Methods:HspBP1 was overexpressed in GFAP-HD transgenic mice,and the expression levels of mHTT and neuropathological related proteins were detected by immunostaining and Western blotting.The motor function level of mice was observed by behavioral experiments.Results:mHTT aggregation in as-trocytes and motor dysfunction occurred in GFAP-HD transgenic mice within a short period of time,but no acti-vation of astrocytes or neuronal damage was observed.Conclusion:HspBP1 can mediate pathological damage by promoting the accumulation of endogenous mHTT in astrocytes,but the coexpression of mHTT in neurons and astrocytes may be essential for significant neuronal degeneration.

关 键 词：亨廷顿病 热休克蛋白70结合蛋白1 星形胶质细胞 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学] R742