Investigation of FadA adhesin from Fusobacterium nucleatum

具核梭杆菌 FadA 粘附素的研究

• 批准号: 10289048
• 负责人: Yiping Han
• 金额: $ 38.09万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10289048
• 关键词: Administrative Supplement; Alzheimer' s Disease; Alzheimer' s disease patient; Amyloid; Amyloid Proteins; Anaerobic Bacteria; Antibodies; Bacterial Adhesins; Binding; Cells; Diagnosis; Etiology; Exhibits; Fusobacterium nucleatum; Future; Grant; In Vitro; Infection; Inflammation; Investigation; Mediating; Oral; Parents; Pathology; Patients; Play; Property; Role; Serum; Specimen; Testing; United States National Institutes of Health; Virulence; in vivo Model; interest; novel; oral anaerobes

Fusobacterium nucleatum (Fn), a Gram-negative anaerobe, is one of the most prevalent oral species associated with extra-oral infections and inflammation, including Alzheimer’s disease (AD). Serum anti-Fn antibody levels have been found to be significantly higher in AD patients compared to the controls. We have recently discovered that the FadA adhesin of Fn exhibits amyloid-like properties. The amyloid-like FadA mediates binding and invasion of host cells. Accumulation of amyloid proteins is a hallmark of AD. Therefore, we hypothesize that amyloid- like FadA plays a role in AD. Testing this hypothesis is a natural extension of our parent R01, which investigates the role of amyloid-like FadA in Fn virulence, yet not focused on AD. Thus, this supplement application is responsive to the following Notice of Special Interest: Alzheimer’s-focused administrative supplements for NIH grants that are not focused on Alzheimer’s disease (NOT-AG-20-034). We propose to examine the presence of Fn and amyloid-like FadA in AD specimens and compare to matched controls. The ability of amyloid- like FadA in inducing AD-associated pathologies will be examined in both in vitro and in vivo models. Results from this study will shed novel lights on the etiology and mechanism of AD.

具核梭杆菌 (Fn) 是一种革兰氏阴性厌氧菌，是最常见的口腔细菌之一。 与口腔外感染和炎症相关的物种，包括阿尔茨海默病 (AD) 已发现 AD 患者的血清抗 Fn 抗体水平显着较高。 与对照相比，我们最近发现 Fn 的 FadA 粘附素表现出。 淀粉样蛋白样特性。 淀粉样蛋白样 FadA 介导宿主细胞的结合和侵袭。 淀粉样蛋白的积累是AD的一个标志，因此，我们认为淀粉样蛋白是AD的一个标志。 就像 FadA 在 AD 中发挥作用一样，测试这个假设是我们的父 R01 的自然延伸， 该研究研究了类淀粉样蛋白 FadA 在 Fn 毒力中的作用，但并未关注 AD。 此补充申请是对以下特别兴趣通知的回应： NIH 资助的以阿尔茨海默病为重点的行政补充，但不重点 阿尔茨海默病 (NOT-AG-20-034) 我们建议检查 Fn 和 Fn 的存在。 AD 样本中的淀粉样蛋白样 FadA 并与匹配对照进行比较。 类似 FadA 诱导 AD 相关病理的作用将在体外和体内进行检查 这项研究的结果将为 AD 的病因和机制提供新的线索。