MICROTUBULE PROTEINS IN ALZHEIMER'S DISEASE

阿尔茨海默病中的微管蛋白

• 批准号: 3809297
• 负责人: LESTER I BINDER
• 金额: --
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3809297
• 关键词: Alzheimer's disease; binding proteins; brain metabolism; calpain; cerebrospinal fluid; developmental neurobiology; embryo /fetus protein; enzyme linked immunosorbent assay; human subject; human tissue; immunocytochemistry; laboratory mouse; microtubule associated protein; microtubules; monoclonal antibody; neurofibrillary tangles; paired helical filament; phosphorylation; postmortem; protein kinase; protein purification; tau proteins; tissue /cell culture; tubulin; western blottings

The microtubule-associated proteins (MAPs), tau and MAP1B are highly regulated during normal neuronal development. Evidence is accumulating suggesting the re-emergence of fetal characteristics in vulnerable neurons involved in Alzheimer's Disease (AD) pathology. Both fetal and adult forms of tau are known to be integral components of the paired helical filament (PHF) and preliminary evidence indicates that Ad-affected neurons express high levels of MAP1B. Therefore, we propose to determine the relative amounts of both of these proteins in brain regions and to determine the fetal/adult tau ratios in AD and control brains. Studies will continue to asses the properties of AD vs control tau and the AD protein, A68. Non- tubulin tau interacting proteins (TIPs), and a newly described 200 kDa tau- like polypeptide will be and quantified in AD and control brain. Microtubule binding studies will be performed using AD and normal soluble tau as well as A68 to ascertain whether these properties are altered in the disease state. In addition, the ability of the AD neuron to metabolize altered tau will be assessed by in vitro protease experiments and the amounts of tau in AD and control CSFs will be determined. Successful completion of these experiments will aid in establishing the degree to which tau, MAP1B and the 200 kDa polypeptide are altered in either their expression, form or interactions in AD pathology.

微管相关蛋白（MAPs），tau蛋白和MAP1B是高度相关的。 在正常神经元发育过程中受到调节。 证据的积累 这表明脆弱神经元中的胎儿特征重新出现， 参与阿尔茨海默病（AD）病理学。 胎儿和成人形式 已知的是成对螺旋丝的组成部分 (PHF)初步证据表明受Ad影响的神经元表达 高水平的MAP1B。 因此，我们建议确定相对 这两种蛋白质在大脑区域的数量，并确定 AD和对照脑中的胎儿/成人tau比率。 研究将继续 评估AD相对于对照tau和AD蛋白A68的性质。 非 微管蛋白tau相互作用蛋白（TIPs），和一个新描述的200 kDa的tau- 类似多肽将在AD和对照脑中定量。 微管结合研究将使用AD和正常可溶性 tau以及A68，以确定这些性质是否在 疾病状态。 此外，AD神经元的代谢能力 改变的tau将通过体外蛋白酶实验进行评估， 测定AD和对照CSF中tau的量。 成功 这些实验的完成将有助于确定 所述tau、MAP1B和200 kDa多肽在其 AD病理学中的表达、形式或相互作用。