Sensitive nerve cells
A massive loss of nerve cells as seen in Parkinson's disease is triggered off only when three conditions are met
In Germany alone, more than 300,000 people are afflicted by Parkinson's disease and the number is growing steadily. However, despite comprehensive research, scientists are still somewhat in the dark as to the molecular changes that trigger this illness. Scientists at the Max Planck Institute of Neurobiology in Martinsried, together with colleagues from Munich and Hamburg, now demonstrated with a new animal model that nerve cells do not begin to die to the extent found in "Parkinson's" until three conditions come together. The results of this study could lead to the development of preventative measures for patients with certain genetic defects, i.e. with a higher predisposition for the disease. These findings are, at any rate, an important step forward in our understanding of this illness. (PloS Biology April 6, 2010)
In the last ten years, various genes that play a role in the outbreak of the hereditary form of Parkinson's disease have been identified. In addition, nerve cell growth factors, such as GDNF, were found to reduce the rate at which nerve cells are destroyed in the brain areas afflicted in Parkinson's disease. However, the hope that this was going to help us towards a better understanding of the disease so far seemed to be unfounded. The treatment with GDNF, as indeed with other, similar growth factors, has not yet left the clinical trial phase. As the brain cells dying in Parkinson's disease are embedded in sensitive brain tissue, their detailed investigation is impossible in humans. The development of animal models in which defined genetic and/or pharmacological manipulations can be made is therefore essential for a good understanding of the molecular and cellular diseases causes. However, a major drawback of Parkinson's research is that so far most animal models fail to display the accelerated loss of nerve cells symptomatic for this illness, thus preventing a thorough analysis of Parkinson's disease mechanisms.
A devastating mixture
Together with colleagues from the Helmholtz Centre in Munich and the Centre for Molecular Neurobiology in Hamburg, scientists from the Max Planck Institute of Neurobiology in Martinsried have now been able to show that a significant cell death in the brain region afflicted in Parkinson's patients occurs only when three conditions join forces. "Although we had an inkling that this might be the case, we had no actual proof up to now", Liviu Aron explains about his study. In a mouse model, three prerequisites had to be fulfilled: a defective disease gene (in this case the DJ-1 gene), a deficiency in responding to a growth factor and the aging of the animal. In other words, nerve cells which lack the DJ-1 gene and which, in addition, cannot react to the pro-survival signals initiated by the growth factor are particularly prone to die as the mouse ages. "The discovered connection between the response to a growth factor and the DJ-1 gene is extremely interesting", adds Rüdiger Klein, the leader of the study. "Environmental factors influence the supply with growth factors and their interactions with genetic factors may help to better understand Parkinson's disease." The analysis of the complex mechanisms that set in during the process of aging is likely to keep scientists busy for some time.
An old association with therapeutic potential?
Complementary genetic investigations into the fruit fly Drosophila revealed that a connection between the growth factor responses and the DJ-1 gene can already be found here. The researchers thus assume that this interaction arose early in evolutionary history and has since then been preserved. This newly discovered connection may open up a new form of therapy for patients with certain genetic defects. Here, a specific medication with GDNF might be more effective in curbing the development of the illness than in other patients. Another vital step towards the goal of finding and fighting the cause of this affliction has been made.