TRANSTHYRETIN AND HEREDITARY AMYLOID NEUROPATHY

甲状腺素运载蛋白和遗传性淀粉样神经病

• 批准号: 3410397
• 负责人: MARIA J SARAIVA
• 金额: $ 3.95万
• 依托单位: NATIONAL INSTITUTE / HEALTH DOUTOR JORGE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-15 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3410397
• 关键词: DNA; European; albumins; amyloidosis; biological polymorphism; cerebrospinal fluid; gene expression; genetic mapping; human tissue; immunologic techniques; laboratory mouse; laboratory rat; monoclonal antibody; mutant; neurons; neurophysiology; peripheral nervous system; receptor; tissue /cell culture

A research program is proposed to investigate in detail the pathogenic mechanisms underlying the Portuguese type of familial amyloidotic polyneuropathy (FAP). This investigation also aims to acquire fundamental new information on the function of transthyretin (TTR) in the nervous system. The results should be relevant for the physiology of the nervous system and provide suggestions for future therapeutic approaches to FAP. Two major projects are proposed. Project One, on the intervening factors in the mechanisms of pathogenesis of FAP, aims to explore the influence of the mutant TTR found in FAP in the etiology of the disease. Studies are proposed to produce a specific monoclonal antibody directed at the mutant TTR and to develop an accurate immunoassay to measure the levels of the mutant TTR in biological specimens. This immunoassay would then be used in a variety of clinical studies to obtain new information about the pathophysiology and pathogenesis of FAP. A large and unique population of patients and carriers of the mutant gene is available in Portugal for these studies. Other studies will aim to localize the mutant TTR in tissues, and to search for DNA polymorphisnes in or adjacent to the TTR gene associated with variations in clinical expression of FAP. The general goal of Project Two is to explore in detail the function and metabolism of TTR in the nervous system. Studies are proposed that aim to: (1) quantitate TTR in the peripheral nerve; (2) explore the distribution and metabolism of TTR in the nervous system (in particular to explore the transfer of TTR from CSF to nerve, and the tissue sites of catabolism of CSF-derived TTR); (3) search for the binding of TTR to components of peripheral nerves; and (4) search for binding of TTR to specific binding sites/receptors of intact.

提出了一个研究计划，详细调查 葡萄牙型家族性 淀粉样多发性神经病（FAP）。 这项调查还旨在 获得关于功能的基本新信息 甲状腺素运载蛋白（TTR）在神经系统中的作用 结果时必须 与神经系统的生理学相关，并提供 对FAP未来治疗方法的建议。 两大 提出了项目。 项目一，关于在发展中国家 FAP的发病机制，旨在探讨FAP的发病机制。 在FAP中发现的突变TTR在FAP病因学中的影响 疾病 研究提出了生产一个特定的单克隆 针对突变TTR的抗体，并开发准确的 用免疫测定法测量小鼠中突变TTR的水平。 生物标本 然后将该免疫测定用于 各种临床研究，以获得新的信息， FAP的病理生理和发病机制。 一个巨大而独特的 患者和突变基因携带者的群体是可用的 在葡萄牙进行这些研究。 其他研究的目的是将 组织中TTR的突变，并寻找DNA多态性， 在TTR基因中或附近， FAP的临床表现。 项目二的总体目标是 详细探讨TTR的功能和代谢， 神经系统 建议研究的目的是：（1）定量 TTR在周围神经中的分布及分布特点 TTR在神经系统中的代谢（特别是为了探索 TTR从CSF转移到神经以及组织部位 CSF衍生的TTR的结合）;（3）寻找 TTR到周围神经的组成部分;和（4）搜索 TTR与完整的特异性结合位点/受体的结合。

项目成果

A new transthyretin mutation associated with amyloid cardiomyopathy.

与淀粉样心肌病相关的新的转甲状腺素蛋白突变。

• 发表时间: 1992
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: Saraiva,MJ;Almeida,MdoR;Sherman,W;Gawinowicz,M;Costa,P;Costa,PP;Goodman,DS
• 通讯作者: Goodman,DS

Prenatal diagnosis of familial amyloidotic polyneuropathy: evidence for an early expression of the associated transthyretin methionine 30.

家族性淀粉样变性多发性神经病的产前诊断：相关转甲状腺素蛋白蛋氨酸 30 早期表达的证据。

• DOI: 10.1007/bf00193586
• 发表时间: 1990
• 期刊: Human genetics
• 影响因子: 5.3
• 作者: Almeida,MR;Alves,IL;Sakaki,Y;Costa,PP;Saraiva,MJ
• 通讯作者: Saraiva,MJ

A new mutation causing familial amyloidotic polyneuropathy.

导致家族性淀粉样多发性神经病的新突变。

• DOI: 10.1016/0006-291x(89)91802-0
• 发表时间: 1989
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Skare,JC;Saraiva,MJ;Alves,IL;Skare,IB;Milunsky,A;Cohen,AS;Skinner,M
• 通讯作者: Skinner,M

Molecular Analyses ofan Acidic Transthyretin Asn90Variant

酸性运甲状腺素蛋白 Asn90 变体的分子分析

• 发表时间: 1991
• 作者: M. Saraiva;M. Almeida;TIsabel LongoAlves;A. Moreira;M. Gawinowicz;P. Costa;S. Rauh;A. Banhzoff
• 通讯作者: A. Banhzoff

Haplotype analysis of common transthyretin mutations.

常见转甲状腺素蛋白突变的单倍型分析。

• DOI: 10.1007/bf00210422
• 发表时间: 1995
• 期刊: Human genetics
• 影响因子: 5.3
• 作者: Almeida,MR;Aoyama-Oishi,N;Sakaki,Y;Holmgren,G;Ulf,D;Ferlini,A;Salvi,F;Munar-Oués,M;Benson,MD;Skinner,M
• 通讯作者: Skinner,M