Potential cause of Parkinson's disease identified

ScienceDaily (Nov. 19, 2012) Deciphering what causes the brain cell degeneration of Parkinson's disease has remained a perplexing challenge for scientists. But a team led by scientists from The Scripps Research Institute (TSRI) has pinpointed a key factor controlling damage to brain cells in a mouse model of Parkinson's disease. The discovery could lead to new targets for Parkinson's that may be useful in preventing the actual condition.

The team, led by TSRI neuroscientist Bruno Conti, describes the work in a paper published online ahead of print on November 19, 2012 by the Journal of Immunology.

Parkinson's disease plagues about one percent of people over 60 years old, as well as some younger patients. The disease is characterized by the loss of dopamine-producing neurons primarily in the substantia nigra pars compacta, a region of the brain regulating movements and coordination.

Among the known causes of Parkinson's disease are several genes and some toxins. However, the majority of Parkinson's disease cases remain of unknown origin, leading researchers to believe the disease may result from a combination of genetics and environmental factors.

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.

Making Connections

Conti and his team 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-13r1 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," said Brad Morrison, then a TSRI postdoctoral fellow and now at University of California, San Diego, who was first author of the paper with Cecilia Marcondes, a neuroimmunologist at TSRI.

Conti agrees: "I thought that these were very interesting coincidences. So we set out to see if we could find any biological significance."

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Potential cause of Parkinson's disease identified