期刊
ACTA NEUROPATHOLOGICA
卷 111, 期 5, 页码 413-421出版社
SPRINGER
DOI: 10.1007/s00401-006-0049-9
关键词
Alzheimer's disease; neurofibrillary tangles; tau protein; granulovacuolar degeneration bodies; casein kinase-1
资金
- NIA NIH HHS [AG018254, AG010161, AG16756, AG14452] Funding Source: Medline
- NIMH NIH HHS [MH/NS31862] Funding Source: Medline
Alzheimer's Disease (AD) is characterized by the appearance of neurofibrillary and granulovacuolar lesions in the brains of affected individuals. The former is composed of hyperphosphorylated aggregates of the microtubule-associated protein tau. The latter is poorly characterized but reacts strongly with anti-phosphoepitope antibodies indicating that it too accumulates phosphoproteins. Both lesions react strongly with antibodies directed against members of the casein kinase-1 family of phosphotransferases, a group of closely related protein kinases that frequently function in tandem with the ubiquitin modification system. To determine whether individual members of the casein kinase-1 family differentially associate with AD lesions, hippocampal sections isolated from late stage cases of AD were subjected to double-label fluorescence immunohistochemistry using a panel of selective anti-casein kinase 1 antibodies and small-molecule fluorochromes thioflavin S and thiazin red. The resultant colocalization patterns revealed that the alpha CK1 isoform strongly correlated with thioflavin S and thiazin red fluorescence, indicating that it preferentially associated with neurofibrillary lesions. In contrast, the delta isoform staining pattern was dominated by colocalization with granulovacuolar degeneration bodies. These findings suggest that granulovacuolar and neurofibrillary lesions occupy separate populations of neurons, and implicate CK1 isoforms in the generation of lesion-associated phosphoepitopes. They also suggest a nexus between the phosphorylation and ubiquitination modifications found in both lesions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据