AGING AND ALZHEIMER DEMENTIA: ROLE OF FIBROUS PROTEIN

该项目旨在了解生物化学，生物学和 阿尔茨海默病和老年痴呆的分子发病机制 阿尔茨海默型（SDAT），两种最常见的神经系统疾病 伴随着衰老。 在这些疾病中，主要的组织病理学病变 是大脑皮层中存在神经纤维缠结 我们有 最近开发了一种方法来纯化SDAT缠结，以高度从 解剖过的大脑 我们计划将纯化后的缠结 生物化学，并比较其氨基酸组成，肽图和 中间丝蛋白的氨基酸序列。 我们将 重点研究两类中间丝蛋白，神经丝蛋白， 三联体蛋白和波形蛋白，它们与 神经纤维缠结 我们将确定是否交联的二， 三酪氨酸或γ-谷氨酰赖氨酸存在于缠结中 蛋白质，最后，我们将研究体外交联的 中间丝蛋白质。 我们将使用亚细胞技术， 分级分离，凝胶电泳，肽图谱，酸水解，凝胶 过滤，高效液相色谱和免疫印迹， 探讨病理性纤维化与正常纤维化的关系 proteins. 从拟议的研究中获得的信息可能会导致 关于这一主要脑损伤原因的进一步致病线索，以及 与疾病的关系。

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.