The most visible signs of Parkinson's disease are caused by the progressive destruction of a comparatively small population of dopamine-generating neurons in the brain. But why these cells? A full answer to that question might lead to ways to block progression of the condition:
Neuroinflammation and its mediators have recently been proposed to contribute to neuronal loss in Parkinson's, but how these factors could preferentially damage dopaminergic neurons has remained unclear until now. [Researchers] were looking for biological pathways that could connect the immune system's inflammatory response to the damage seen in dopaminergic neurons. After searching human genomics databases, the team's attention was caught by a gene encoding a protein known as interleukin-13 receptor alpha 1 chain (IL-13Ra1), as it is located in the PARK12 locus, which has been linked to Parkinson's.
IL-13rα1 is a receptor chain mediating the action of interleukin 13 (IL-13) and interleukin 4 (IL-4), two cytokines investigated for their role as mediators of allergic reactions and for their anti-inflammatory action. With further study, the researchers made the startling discovery that in the mouse brain, IL-13Ra1 is found only on the surface of dopaminergic neurons. "This was a 'Wow!' moment."
The scientists set up long-term experiments using a mouse model in which chronic peripheral inflammation causes both neuroinflammation and loss of dopaminergic neurons similar to that seen in Parkinson's disease. The team looked at mice having or lacking IL-13Ra1 and then compared the number of dopaminergic neurons in the brain region of interest. The researchers expected that knocking out the IL-13 receptor would increase inflammation and cause neuronal loss to get even worse. Instead, neurons got better.
If further research confirms the IL-13 receptor acts in a similar way in human dopaminergic neurons as in mice, the discovery could pave the way to addressing the underlying cause of Parkinson's disease. Researchers might, for instance, find that drugs that block IL-13 receptors are useful in preventing loss of dopaminergic cells during neuroinflammation.