Do allergens contribute to neurodegeneration?

摘要 帕金森病(PD)是第二常见的神经退行性疾病，影响约1%的 60岁以上的人口，仅在美国每年就有大约5万例新病例报告。基因研究已经 确定了至少9个罕见的单基因帕金森病病因和13个以上的遗传位点。然而，大多数帕金森病患者的病因尚不清楚。 并被认为是环境和遗传因素共同作用的结果。这些组合的识别 仍然是一个重大挑战。在这里，我们建议检验这样一个假设，即一种组合由过敏反应表示 (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 临床研究提供了高度过敏反应和帕金森病易感性之间的强烈联系，以及我们最近的 发现过敏反应的关键调节因子IL-13和IL-13Rα1与人类帕金森病有关，并与神经元有关 帕金森病小鼠模型的丢失。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，以预防帕金森病或减少其进展。抗过敏药 治疗方法，包括特定的IL-13中和抗体，已经可用或正在开发中，这将 减少基础研究、治疗剂开发和临床应用之间的时间延迟。此外， 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。 帕金森病和神经退行性疾病中的炎症和过敏。

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.