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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 在阿尔茨海默病（AD）和许多其他引起痴呆的疾病中发生的可见神经元病理由微管结合蛋白tau的聚合形式组成。 总的来说，这些疾病被称为“tau蛋白病”，并且代表人类痴呆的主要原因。当tau（一种在溶液中几乎没有有序结构的分子）聚合成明显有序的细丝时，就会发生这种病理。 Tau丝可以呈现“直的”（单个）或成对的螺旋形式。这种自组装现象本身作为一种生物物理过程是令人感兴趣的，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tau蛋白病（AD、皮克病、进行性核上性麻痹（PSP）、皮质基底节变性（CBD）、FTDP-17痴呆等）（Lee，V.，等Ann. Rev. Neurosci. 24：1121-1159，2001），通过明显相似的机制的其他蛋白质的聚集是几种其他神经变性疾病的特征。 因此，了解tau聚合的方式和原因不仅可以为开发针对AD的治疗剂开辟道路，还可以为开发治疗更广泛的神经退行性疾病的化合物开辟道路。 在Bio-CAT获得的初步数据确定了以前在纯化的NFT中观察到的衍射图案，并且还确定了许多新的结构特征，以及组织形态和NFT方向之间的对应关系。

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.