Do allergens contribute to neurodegeneration?

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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.