Taddei N, Liguri G, Sorbi S, Amaducci L, Camici G, Nassi P, Cecchi C, Ramponi G
Department of Biochemical Sciences, University of Florence, Italy.
Neurosci Lett. 1993 Mar 19;151(2):158-61. doi: 10.1016/0304-3940(93)90010-i.
A study concerning the amount of soluble ubiquitin in different cortical and subcortical regions of brains from patients with Alzheimer's disease compared to the amount in normal brains is presented. Several samples from 9 brain regions were processed and analyzed by liquid chromatography. In almost all the investigated cerebral regions the soluble ubiquitin content was significantly higher in pathologic tissue than in normal tissue. The primary structure of ubiquitin isolated from brain tissue affected by Alzheimer's degenerative processes was determined and resulted to be identical to normal human ubiquitin. These findings, together with the detection of polyubiquitinated proteins in paired helical filaments of neurofibrillary tangles described by several authors, suggest that an impairment of the process of intracellular, ubiquitin-dependent proteolysis might play an important role in the pathogenesis of this neurodegenerative disease. On the other hand, the expression of the correct polypeptide sequence in brain with Alzheimer's disease seems to exclude a mutation of the polyubiquitin gene as a cause of these alterations.
本文呈现了一项关于阿尔茨海默病患者大脑不同皮质和皮质下区域中可溶性泛素含量与正常大脑中该含量对比的研究。从9个脑区采集了多个样本，并通过液相色谱法进行处理和分析。在几乎所有被研究的脑区中，病理组织中的可溶性泛素含量显著高于正常组织。对从受阿尔茨海默病退行性病变影响的脑组织中分离出的泛素的一级结构进行了测定，结果显示其与正常人类泛素相同。这些发现，连同多位作者所描述的在神经原纤维缠结的双螺旋丝中检测到多聚泛素化蛋白，表明细胞内依赖泛素的蛋白水解过程受损可能在这种神经退行性疾病的发病机制中起重要作用。另一方面，阿尔茨海默病大脑中正确多肽序列的表达似乎排除了多聚泛素基因突变是这些改变的原因。
