IL-13Ra1 and Neuroinflammatory Damage in the MPTP Pre-Clinical Model of PD
Target Validation, 2013
Neuroinflammation has been proposed to contribute to both the pathogenesis and the progression of Parkinson's disease (PD). We recently showed that an important modulator of peripheral inflammation, the interleukin 13 receptor alpha 1 (IL-13Rα1), is expressed in brain dopaminergic (DA) neurons, the same neurons that are lost in PD. We also found that IL-13Rα1 increases the susceptibility of DA neurons to oxidative damage in an inflammatory model, suggesting that IL-13Rα1 may play a role in the pathogenesis of PD. Here, we aim to determine the extent to which IL-13Ra1 contributes to the progression of PD. We also aim to identify the cellular sources of endogenous IL-13Rα1 activators.
We propose to measure and compare the number of DA neurons in pre-clinical models with or without IL-13Rα1 treated with MPTP, a neurotoxin that causes a syndrome clinically and pathologically indistinguishable from PD. We will also carry out a comparative evaluation of the neuroinflammatory response that is typically associated with MPTP. Finally, we will determine the cellular source and time course of IL-13 and IL-4 expression, two cytokines that can activate IL-13α1 signaling.
Impact on Diagnosis/Treatment of Parkinson's Disease:†††††††††††††
IL-13Rα, its endogenous ligands and the cells that produce them may represent novel therapeutic targets for PD.†The "IL-13 system" is an attractive drug target due to its role in mediating allergic reactions; compounds to block its action are already under development. The data collected from the experiments proposed here will help us determine whether targeting the "IL-13 system" represents a novel strategy to treat PD.
Next Steps for Development:††††††††††
We expect to determine the extent to which IL-13Rα1 contributes to the progression of DA neuronal loss. In addition, we expect to identify the cellular source of the endogenous activators of IL-13Rα1 signaling, IL-13 and IL-4. †
Location: La Jolla, California, United States