ALZHEIMER'S DISEASE: MODELING PATHOLOGIC STRAIN-LIKE VARIANTS OF MULTIMERIC A?

阿尔茨海默病：模拟多聚体 A 的病理菌株样变体？

• 批准号: 8172438
• 负责人: LARY C WALKER
• 金额: $ 2.74万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172438
• 关键词: Affinity; Alzheimer' s Disease; Alzheimer' s disease model; Amino Acid Sequence; Binding; Binding Sites; Computer Retrieval of Information on Scientific Projects Database; Disease; Funding; Grant; Human; Institution; Investigation; Nature; Pathologic; Pittsburgh Compound-B; Research; Research Personnel; Resources; Shapes; Site; Source; United States National Institutes of Health; Variant; nonhuman primate; protein aggregate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the past year, we have continued and expanded our analysis of strain-like structural variants of multimeric aggregates of the protein A¿. We have shown that, unlike in Alzheimer's disease, naturally occurring A¿ in nonhuman primates does not bind the A¿-binding ligand PIB with high affinity, despite an identical amino acid sequence. This finding suggests that PIB may recognize a polymorphic site on multimeric A¿. Unexpectedly, in the course of this investigation, we also discovered a single case of Alzheimer's disease with very high A¿ levels, yet negligible high-affinity PIB binding, indicating that the binding site may vary among humans with the disease. The findings support growing evidence that protein aggregates may assume several multidimensional shapes that could govern their pathogenic nature.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在过去的一年中，我们继续并扩大了对 A 蛋白多聚体的菌株样结构变异的分析。 我们已经证明，与阿尔茨海默氏病不同，非人灵长类动物中天然存在的A′尽管具有相同的氨基酸序列，但并不以高亲和力结合A′结合配体PIB。这一发现表明 PIB 可能识别多聚体 A¿ 上的多态性位点。 出乎意料的是，在这项研究过程中，我们还发现了一个阿尔茨海默病病例，其 A¿ 水平非常高，但高亲和力 PIB 结合却可以忽略不计，这表明该疾病患者的结合位点可能有所不同。这些发现支持越来越多的证据表明蛋白质聚集体可能呈现多种多维形状，从而控制其致病性质。