X-RAY STUDIES OF NEUROFIBRILLARY TANGLES IN ALZHEIMER'S DISEASE BRAIN TISSUE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 阿尔茨海默病(AD)和其他一些导致痴呆的疾病中出现的可见神经元病理是由微管结合蛋白tau的聚合形式组成的。总而言之，这些疾病被称为“tauopathies”，是导致人类痴呆症的主要原因。当tau分子在溶液中几乎没有有序结构，聚合成明显有序的细丝时，就会发生这种病理。牛磺酸纤维可以呈“直”状(单)或成对螺旋状。这种自组装现象本身就是一种生物物理过程，但由于其机制与大量人类神经退行性疾病的潜在相关性，这种兴趣变得更加尖锐。类似于tauopathies(AD、Pick病、进行性核上性麻痹(PSP)、皮质基底性变性(CBD)、FTDP-17痴呆等)(Lee，V.，et al Ann)。神经科学牧师。24：1121-1159,2001)，通过明显相似的机制聚集其他蛋白质是其他几种神经退行性疾病的特征。因此，了解tau是如何以及为什么聚合的，不仅可以为开发针对AD的治疗剂开辟道路，也可以为治疗更广泛的神经退行性疾病的化合物开辟道路。Bio-CAT获取的初步数据确定了以前在纯化的NFT中看到的衍射图案，还确定了一些新的结构特征，以及组织形态和NFT取向之间的对应关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The visible neuronal pathology that occurs in Alzheimer's disease (AD) and a number of other dementia-causing diseases is composed of a polymerized form of the microtubule-binding protein, tau. Collectively, these diseases are termed "tauopathies" and represent the predominant cause of human dementia. This pathology occurs when tau, a molecule that possesses little ordered structure in solution, polymerizes into an apparently well-ordered filament. Tau filaments can take on "straight" (single) or paired helical forms. This self-assembly phenomenon is of interest in its own right as a biophysical process, but this interest is made more acute by the potential relevance of its mechanism to a large number of human neurodegenerative disorders. Similar to the tauopathies (AD, Pick disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), FTDP-17 dementias, and others)(Lee, V., et al Ann. Rev. Neurosci. 24:1121-1159, 2001), aggregation of other proteins by demonstrably similar mechanisms is a characteristic of several other neurodegenerative diseases. Thus, understanding how and why tau polymerizes could open avenues for the development not only of therapeutic agents directed at AD, but at compounds to treat the broader base of neurodegenerative diseases.. Preliminary data taken at Bio-CAT identified diffraction patterns seen previously in purified NFTs, and also identified a number of new structural features, as well as a correspondence between tissue morphology and NFT orientation.