AMYLOID DEPOSITION ALZHEIMER'S DISEASE

淀粉样蛋白沉积 阿尔茨海默病

• 批准号: 3120104
• 负责人: PETER T LANSBURY
• 金额: $ 16.33万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-12 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3120104
• 关键词: Alzheimer's disease; amyloid proteins; biophysics; chemical aggregate; chemical binding; chemical kinetics; chemical stability; chemical structure function; conformation; dipole moment; dyes; hydrogen bond; infrared spectrometry; inhibitor /antagonist; interferometry; intermolecular interaction; light scattering; method development; nuclear magnetic resonance spectroscopy; peptide analog; peptide chemical synthesis; peptide structure; physical model; protein sequence; protein structure; protein structure function; substance P; synthetic peptide

Amyloid deposition in the brain is considered to be a marker for Alzheimer's disease, although a causal relationship has not been proven. The amyloid protein has not been available for study due to practical problems with its purification. In addition, current biophysical methods are not suited for the characterization of insoluble, noncrystalline proteins such as the amyloid proteins. Our work has focussed on these two problems. We have been successful in developing a synthetic route to the 0 protein which is amenable to scale-up. A novel biophysical approach (solid-state NMR and FTIR) has allowed us to observe details in amyloid structure which have heretofore escaped detection. We propose to continue the development of this approach. Our goal is to fully determine the molecular structure of the protein amyloid. We also are interested in using this structural information to design molecules which bind to amyloid (analogs of Congo red) and/or inhibit amyloid formation (conformationally-restrained peptide analogs). Finally, we hope to determine the sequence requirements for amyloid formation by comparing sequences from various amyloid-forming proteins.

大脑中的淀粉样蛋白沉积被认为是 阿尔茨海默氏症，尽管因果关系尚未得到证实。 由于实际情况，淀粉样蛋白还不能用于研究。 它的提纯有问题。此外，目前的生物物理方法 不适合描述不溶的、非晶态的 蛋白质，如淀粉样蛋白。我们的工作主要集中在这两个方面 有问题。我们已经成功地开发出了一条通向0的合成路线 可放大的蛋白质。一种新的生物物理方法 (固态核磁共振和FTIR)使我们能够观察淀粉样蛋白的细节 到目前为止都未被检测到的结构。我们建议继续 这一方法的发展。我们的目标是充分确定 淀粉样蛋白的分子结构。 我们也有兴趣利用这些结构信息来设计 结合淀粉样蛋白(刚果红的类似物)和/或抑制的分子 淀粉样蛋白形成(构象受抑制的多肽类似物)。最后， 我们希望通过以下方法确定淀粉样蛋白形成的序列要求 比较各种淀粉样蛋白的序列。