认知障碍以萎缩退行性疾病及脑血管疾病所致为主。萎缩退行性疾病以痴呆为主要表现的有阿尔茨海默病(Alzheimer’s disease,AD)、路易体痴呆(dementia with Lewy bodies,DLB)及额颞叶痴呆等;脑血管病以认知障碍为主要表现的是脑小血管病...认知障碍以萎缩退行性疾病及脑血管疾病所致为主。萎缩退行性疾病以痴呆为主要表现的有阿尔茨海默病(Alzheimer’s disease,AD)、路易体痴呆(dementia with Lewy bodies,DLB)及额颞叶痴呆等;脑血管病以认知障碍为主要表现的是脑小血管病,约占血管性痴呆的2/3。认知领域受到国内外的瞩目,近年国际上又更新了AD及DLB的诊治共识,我国也推出了脑小血管病认知障碍诊治指南,述评如下。展开更多
Huntington＇s disease （HD） is caused by abnormal CAG repeat expansion in the 5＇-end of the Huntingtin （HTT） gene. In addition to the canonical C-terminal full-length huntingtin （htt） nuclear export signal, a cy...Huntington＇s disease （HD） is caused by abnormal CAG repeat expansion in the 5＇-end of the Huntingtin （HTT） gene. In addition to the canonical C-terminal full-length huntingtin （htt） nuclear export signal, a cytoplasmic localization-related domain （CLRD） in the N-terminus of htt has recently been reported. Here, we analyzed this domain by introducing deletion and substitution mutations in a truncated N-terminal htt protein and subsequently monitored htt expression, aggregation and subcellular localization by immunocytochemistry and Western blot analysis. We demonstrated that Htt1-17 was the essential sequence for htt cytoplasmic localization. We also found that the subcellular distribution of htt was altered when Htt1_17 was mutated to contain amino acids of different charges, suggesting a structural requirement of Htt1-17 for the cytoplasmic localization of htt. Deletion of the first three amino acids did not affect its association with mitochondria. We observed that defective cytoplasmic localization resulted in a reduction of total htt aggregates and increased nuclear aggregates, indicating that the subcellular distribution of the protein might influence the aggregation process. These studies provide new insight into the molecular mechanism of htt aggregation in HD.展开更多
文摘认知障碍以萎缩退行性疾病及脑血管疾病所致为主。萎缩退行性疾病以痴呆为主要表现的有阿尔茨海默病(Alzheimer’s disease,AD)、路易体痴呆(dementia with Lewy bodies,DLB)及额颞叶痴呆等;脑血管病以认知障碍为主要表现的是脑小血管病,约占血管性痴呆的2/3。认知领域受到国内外的瞩目,近年国际上又更新了AD及DLB的诊治共识,我国也推出了脑小血管病认知障碍诊治指南,述评如下。
基金supported by the National Natural Science Foundation of China(Grant Nos.30770761 and 30971000)
文摘Huntington＇s disease （HD） is caused by abnormal CAG repeat expansion in the 5＇-end of the Huntingtin （HTT） gene. In addition to the canonical C-terminal full-length huntingtin （htt） nuclear export signal, a cytoplasmic localization-related domain （CLRD） in the N-terminus of htt has recently been reported. Here, we analyzed this domain by introducing deletion and substitution mutations in a truncated N-terminal htt protein and subsequently monitored htt expression, aggregation and subcellular localization by immunocytochemistry and Western blot analysis. We demonstrated that Htt1-17 was the essential sequence for htt cytoplasmic localization. We also found that the subcellular distribution of htt was altered when Htt1_17 was mutated to contain amino acids of different charges, suggesting a structural requirement of Htt1-17 for the cytoplasmic localization of htt. Deletion of the first three amino acids did not affect its association with mitochondria. We observed that defective cytoplasmic localization resulted in a reduction of total htt aggregates and increased nuclear aggregates, indicating that the subcellular distribution of the protein might influence the aggregation process. These studies provide new insight into the molecular mechanism of htt aggregation in HD.
