AGING AND ALZHEIMER DEMENTIA: ROLE OF FIBROUS PROTEIN

这个项目的目的是了解生物化学，生物学和 阿尔茨海默病与老年性痴呆的分子发病机制 阿尔茨海默型(SDAT)，两种最常见的神经疾病 伴随着衰老。在这些疾病中，主要的组织病理损害 大脑皮层中存在神经原纤维缠结。我们有 最近开发了一种从SDAT纠缠中高度纯化SDAT纠缠的方法 尸检的大脑。我们计划对提纯的纠缠进行表征 生物化学，并比较它们的氨基酸组成、肽图和 氨基酸序列与中间丝蛋白的氨基酸序列一致。我们会 重点研究两类中间丝蛋白--神经丝 三联体蛋白和波形蛋白，具有相同的免疫学特性 神经原纤维缠结。我们将确定Di-， 三酪氨酸或β(谷氨酰基)赖氨酸存在于缠结中 蛋白质，最后，我们将研究体外交联剂 中间丝蛋白。我们将使用亚细胞等技术 分级、凝胶电泳法、肽图、酸水解法、凝胶 过滤、高效液相色谱和免疫印迹 病理性纤维与正常纤维关系的研究 蛋白质。从拟议的研究中获得的信息可能会导致 关于这一重大脑部病变原因的进一步病原学线索，以及 它与这种紊乱的关系。

This project is aimed at understanding the biochemistry, biology and molecular pathogenesis of Alzheimer's disease and senile dementia of the Alzheimer type (SDAT), the two most common neurological disorders accompanying aging. In these disorders, the main histopathological lesion is the presence of neurofibrillary tangles in the cerebral cortex. We have recently developed a method to purify SDAT tangles to a high degree from autopsied brains. We plan to characterize the purified tangles biochemically, and compare their amino acid compositions, peptide maps and amino acid sequences to that of intermediate filament proteins. We will focus on two classes of intermediate filament proteins, neurofilament triplet proteins and vimentin, which share immunological properties with neurifibrillary tangles. We will determine whether cross-links of di-, tri-tyrosine or Epsilon (Gamma-glutamyl) lysine are present in the tangle proteins, and finally we will investigate the invitro cross-linking of intermediate filament proteins. We will use techniques such as subcellular fractionation, gel electrophoresis, peptide mapping, acid hydrolysis, gel filtration, high performance liquid chromatography and immunoblotting to study the relationship between the pathological and normal fibrous proteins. The information obtained from the studies proposed might lead to further pathogenic clues as to the cause of this major cerebral lesion, and its relation to the disorder.