TRANSTHYRETIN AND HEREDITARY AMYLOID NEUROPATHY

提出了一个研究计划，以详细调查 葡萄牙型家族性红斑狼疮的发病机制 淀粉样多发性神经病(FAP)。这项调查还旨在 获取有关……功能的基本新信息 神经系统中的转甲状腺素(TTR)。结果应该是 与神经系统的生理学有关，并提供 对FAP未来治疗方法的建议。两大 提出了项目建议。项目一，关于#年的干预因素 探讨FAP的发病机制，旨在探讨FAP的发病机制。 FAP中发现的突变型TTR区在慢性阻塞性肺疾病发病中的作用 疾病。有人建议进行研究，以生产一种特定的单克隆 针对突变体TtR的抗体并开发出准确的 免疫测定法检测人外周血中突变型TtR水平 生物标本。然后，这种免疫分析将被用于 各种临床研究，以获得有关 FAP的病理生理及发病机制。一个巨大而独特的 突变基因的患者和携带者的人群是可用的 在葡萄牙进行这些研究。其他研究将致力于本地化 组织中的突变型TTR，并寻找DNA多态性 在与基因变异相关的TTR基因中或在其附近 FAP的临床表达。第二个项目的总体目标是 详细探讨TTR在机体中的功能和代谢。 神经系统。提出的研究目的是：(1)量化 (2)探讨其在周围神经中的分布和分布。 Ttr在神经系统中的代谢(特别是探索 脑脊液到神经的TTR转移及其组织部位 脑脊液来源的TTR的分解代谢)；(3)寻找结合 外周神经成分的TTR；以及(4)搜索 TTR与完整的特定结合部位/受体的结合。

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.