Do allergens contribute to neurodegeneration?

过敏原会导致神经退行性变吗？

• 批准号: 10542643
• 负责人: BRUNO CONTI
• 金额: $ 22.19万
• 依托单位: SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-16 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10542643
• 关键词: Do; allergens; contribute; neurodegeneration

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disorder and affects approximately 1% of the population over the age of 60, with about 50,000 new cases reported annually in the U.S. alone. Genetic studies have identified at least 9 rare, monogenic causes of PD and over 13 genetic loci. Yet, most PD cases remain of unknown origin and are believed to result from a combination of environmental and genetic factors. The identification of these combinations remains a major challenge. Here we propose to test the hypothesis that one combination is represented by allergic reaction (environmental) and the receptor α1 for the interleukin 13 (IL-13Rα1) (genetic). Our hypothesis is supported by a human clinical study providing a strong link between heightened allergic response and susceptibility to PD, as well as by our recent finding that pivotal regulators of allergic reactions, IL-13 and IL-13Rα1, are linked to human PD and contribute to neuronal loss in mouse models of PD. If successful, we will identify allergic reactions and the IL-13 system as novel pathogenic components of PD and will utilize them as novel therapeutic targets to prevent PD or reduce its progression. Anti-allergic therapies, including specific IL-13 neutralizing antibodies, are already available or are under development, which will reduce the time delay between basic research, development of therapeutic agents, and their clinical use. In addition, the animal model will provide a new experimental tool for the scientific community to further understand the role of inflammation and allergy in PD and neurodegenerative diseases.

抽象的 帕金森病 (PD) 是第二常见的神经退行性疾病，影响约 1% 的人 60 岁以上人群，仅在美国每年就报告约 50,000 例新病例。 确定了至少 9 种罕见的单基因帕金森病病因和超过 13 个基因位点，但大多数帕金森病病例的起源仍不明。 并被认为是环境和遗传因素共同作用的结果。 仍然是一个重大挑战，在这里我们建议测试一种假设，即过敏反应代表一种组合。 （环境）和白介素 13 受体 α1 (IL-13Rα1)（遗传）我们的假设得到了人类的支持。 临床研究提供了过敏性过敏反应与帕金森病易感性之间的密切联系，以及我们最近的研究 发现过敏反应的关键调节因子 IL-13 和 IL-13Rα1 与人类 PD 相关，并有助于神经元 如果成功，我们将确定过敏反应和 IL-13 系统为新的致病因素。 帕金森病的成分，并将利用它们作为新的治疗靶点来预防帕金森病或减少其进展。 包括特定 IL-13 中和抗体在内的疗法已经可用或正在开发中，这将 减少基础研究、治疗药物开发及其临床使用之间的时间延迟。 动物模型将为科学界进一步了解其作用提供新的实验工具 PD 和神经退行性疾病中的炎症和过敏。