AMYLOID PRECURSOR IN ALZHEIMERS DISEASE

阿尔茨海默病中的淀粉样前体

• 批准号: 2049785
• 负责人: GEORGE PERRY
• 金额: $ 2.9万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2049785
• 关键词: Alzheimer's disease; actin binding protein; amyloid proteins; antibody; chemical binding; epitope mapping; heparin; human tissue; implant; laboratory rat; neuritic plaques; neurofibrillary tangles; neurofilament; paired helical filament; proteins; proteoglycan; western blottings

DESCRIPTION: (Adapted from the applicant's abstract) Although with the cloning of the cDNA for the amyloid precursor protein (APP) in late 1986 the sequences and identification of APP have been possible, the importance of APP in the pathogenesis of Alzheimer Disease (AD) is essentially unknown. During the previous funding period, several immunochemical and biochemical probes were produced and used by this laboratory to conclude that neurons are the major source of APP in the senile plaque, the site of the amyloid deposition. They suggest these findings are directly relevant to their original hypothesis: that the intraneuronal cytoskeletal changes of AD, neurofibrillary pathology (NFP), is a direct result of the interaction of APP with the cytoskelton. The finding that NFP contains abundant heparin sulfate proteoglycans (HSPG) gave them a chemical basis for this binding, since APP is an ASPG binding protein. In binding studies, they found that many NFP components specifically associate with APP accumulations. Support was therefore found for the hypothesis that NFP components are incorporated through reciprocal binding. In the present proposal, they will extend these studies through the following aims: (1) Binding studies that will define NFP's biochemistry in situ as well as traditional biochemical properties; (2) determine whether HSPG's are associated with the NFP's of other diseases; (3) determine the relationship of neuritic change to amyloid deposition in AD and control brains; (4) study the effect of APP gradients in the brain through brain implants of APP and B-protein; (5) physical mapping of NFP epitopes.

描述：（改编自申请人的摘要）虽然与 1986年底克隆了淀粉样前体蛋白（APP）的cDNA APP的序列和鉴定已经成为可能， APP在阿尔茨海默病（AD）发病机制中的作用本质上是 未知 在上一个供资期间，一些免疫化学和 该实验室生产并使用了生化探针， 神经元是老年斑中APP的主要来源，老年斑是 淀粉样沉积他们认为这些发现与 他们最初的假设：神经元内细胞骨架的变化 AD的神经病理学（NFP）是AD的直接结果， APP与细胞因子的相互作用。 发现NFP含有 丰富的硫酸肝素蛋白多糖（HSPG）为它们提供了化学基础 因为APP是ASPG结合蛋白。 的结合 研究发现，许多NFP成分与 APP积累。 因此，有人支持以下假设， NFP组分通过相互结合并入。 在 根据目前的建议，他们将通过以下方式扩展这些研究 目的：（1）结合研究，将NFP的生物化学定义为 以及传统的生化特性;（2）确定HSPG是否 与其他疾病的NFP相关;（3）确定 AD和对照组神经炎性改变与淀粉样蛋白沉积的关系 （4）研究APP梯度在脑内的作用 APP和B蛋白的植入物;（5）NFP表位的物理作图。

项目成果

Advanced Maillard reaction end products, free radicals, and protein oxidation in Alzheimer's disease.

阿尔茨海默病中的高级美拉德反应终产物、自由基和蛋白质氧化。

• DOI: 10.1111/j.1749-6632.1994.tb21836.x
• 发表时间: 1994
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Smith,MA;Richey,PL;Taneda,S;Kutty,RK;Sayre,LM;Monnier,VM;Perry,G
• 通讯作者: Perry,G

Amyloid precursor protein in senile plaques of Alzheimer disease.

阿尔茨海默病老年斑中的淀粉样前体蛋白。

• DOI: 10.1016/s0140-6736(88)90219-x
• 发表时间: 1988
• 期刊: Lancet (London, England)
• 作者: Perry,G;Lipphardt,S;Mulvihill,P;Kancherla,M;Mijares,M;Gambetti,P;Sharma,S;Maggiora,L;Cornette,J;Lobl,T
• 通讯作者: Lobl,T

Alteration of neuritic cytoarchitecture in Alzheimer disease.

阿尔茨海默病神经炎细胞结构的改变。

• 发表时间: 1989
• 期刊: Progress in clinical and biological research
• 作者: Onorato,M;Mulvihill,P;Connolly,J;Galloway,P;Whitehouse,P;Perry,G
• 通讯作者: Perry,G

Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer's disease.

阿尔茨海默病神经原纤维病理学中神经丝蛋白的羰基相关翻译后修饰。

• DOI: 10.1046/j.1471-4159.1995.64062660.x
• 发表时间: 1995
• 期刊: Journal of neurochemistry
• 影响因子: 4.7
• 作者: Smith,MA;Rudnicka-Nawrot,M;Richey,PL;Praprotnik,D;Mulvihill,P;Miller,CA;Sayre,LM;Perry,G
• 通讯作者: Perry,G

Immunochemical demonstration of tropomyosin in the neurofibrillary pathology of Alzheimer's disease.

• 发表时间: 1990
• 期刊: The American journal of pathology
• 作者: P. Galloway;P. Mulvihill;S. Siedlak;M. Mijares;M. Kawai;H. Padget;R. Kim;George Perry