Neuronal interleukin 13 receptor and parkinson’s disease

International Congress on Neuroimmunology and Therapeutics

DoubleTree by Hilton Hotel San Francisco Airport, San Francisco, CA, USA

Bruno Conti

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

Neuroinflammation is believed to contribute to the onset and/or the progression of Parkinsonâ??s Disease (PD). However, inflammatory mediators contribution to the preferential loss of dopaminergic (DA) neurons remains poorly understood. In order to investigate the pathophysiological role of inflammation in PD, we analyzed the existance of a possible linkage between mediators of infammation and genetic loci associated with PD. We found that the gene encoding for interleukin 13 receptor alpha 1 (IL-13Ra1) lies on the human X chromosome at Xq24 within the Xq21-q25 region found to contain the PARK12 locus of PD susceptibility. IL-13Ra1 is the subunit of a heterodimeric receptor that is responsible for mediating the action of the Th2 cytokines; IL-13 and IL-4. These cytokines are known as important peripheral modulators of allergic reactions, of anti-helmintic response and also for their anti-inflammatory action. Investigation into the distribution of IL-13Ra1 in the mouse brain reveals that it is expressed in the dopaminergic neurons of the substantia nigra pars compacta (SNpC) and the ventral tegmental area (VTA). Thus we hypothesized that neuronal IL-13Ra1 may influence dopaminergic cells survival and functions and tested our hypothesis using mice null for IL-13Ra1 (Il13ra1-/Y). Il13ra1-/Y and Il13ra1+/Y had similar number of dopaminergic neurons in the SNc and the VTA and had comparable levels of dopamine. However, Il13ra1-/Y animals were protected from loss of DA neurons in a neurotoxic insult as well as in a chronic peripheral inflammation mouse model of PD. In vitro studies showed that while IL-13 and IL-4 did not have any intrinsic toxic effect when administered alone, they greatly potentiated the cytotoxicity of reactive oxygen species. Our finidng indicates that neuronal IL-13Ra1 can contribute to the preferential loss of DA neurons during neuroinflammation and may be involved in the pathogenesis and/or the progression of PD.