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Environment Meets Genetics: New Findings About Parkinson’s Disease

Jülich, 23 December 2016 – The causes of Parkinson’s disease have been the subject of intensive research for decades. A German–Argentinian team of scientists, in which Jülich is involved, has now found out that an interplay of genetic factors and certain metals could play an important role. They discovered that the interaction with copper crucially alters the behaviour of a specific protein. The findings of the study, which have been published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS), open up completely new perspectives for therapeutic approaches.

Parkinson’s affects many millions of people worldwide. The disease is known for its typical motor symptoms such as tremor, muscular rigidity, and the slowing of physical movements. It is also characterized, however, by a multitude of non-motor problems that can also be highly debilitating.

Currently available therapies only treat the symptoms; little is known about the actual causes of the disease. The onset of Parkinson’s very often occurs spontaneously, with the risk of developing the disease generally rising with increasing age. It is only in a small proportion of patient cases, roughly 5–10 %, that a genetic predisposition is assumed to be the cause. Environmental factors, such as pesticides and metals, are suspected of increasing the risk of developing the disease.

Can a single protein contribute to a better understanding of Parkinson’s?

Scientists who investigated the brains of patients found an accumulation of protein clumps of alpha-synuclein. The small, soluble protein occurs in the brain of vertebrates and was first associated with Parkinson’s disease 20 years ago. To this day, it remains the subject of scientific research.

A joint study by University Medical Center Göttingen, the Max Planck Institute for Biophysical Chemistry, the IIDEFAR institute in Rosario, Argentina, and Forschungszentrum Jülich was able to gain new insights into the functioning of alpha-synuclein. The scientists discovered interactions with environmental factors that contribute to an aggregation of the proteins.

The researchers from Göttingen found that the interplay of copper ions and a particular form of alpha-synuclein, known as H50Q, influences the probability of protein aggregation. Copper is a metal that is associated with neurodegeneration – the progressive loss of nerve cells. H50Q is a pathogenic mutation that was discovered in a number of patients. Prof. Paolo Carloni and his colleagues Jun.-Prof. Giulia Rossetti and Enrique Abad have now been able to show how the two factors interact using the combination of structural data and simulations on Jülich supercomputers.

More than ten million core hours on Jülich supercomputers

"It is very important to combine quantum and molecular mechanics simulation techniques,” explains Jun.- Prof. Rossetti. “Using these techniques, it is possible to predict complex interactions and spectroscopic properties of certain proteins and metal ions." Access to the supercomputing infrastructure at Forschungszentrum Jülich was a crucial advantage, says Prof. Carloni. "Our simulations of copper ions bonded to alpha-synuclein required more than ten million core hours."

Original publication:

Villar-Piqué A., Lopes da Fonseca T., Sant’Anna R., Szegö E.M., Fon-seca-Ornelas L., Pinho R., Carija A., Gerhardt E., Masaracchia C., Abad Gonzalez E., Rossetti G., Carloni P., Fernández C.O., Foguel D., Milosevic I., Zweckstetter M., Ventura S., Outeiro T.F.: Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity. PNAS (2016), 113(42): E6506-6515.

Further information:

Institute for Advanced Simulations – Computational Biomedicine (IAS-5/INM-9)

Contacts:

Jun.-Prof. Giulia Rossetti
Institute for Advanced Simulations – Computational Biomedicine (IAS-5/INM-9)
Tel: +49 2461 61-8933
Email: g.rossetti@fz-juelich.de

Prof. Paolo Carloni
Institute for Advanced Simulations – Computational Biomedicine (IAS-5/INM-9)
Tel: +49 2461 61-8942
Email: p.carloni@fz-juelich.de

Press contacts:

Dr. Regine Panknin
Corporate Communications
Tel: +49 2461 61-9054
Email: r.panknin@fz-juelich.de

Erhard Zeiss
Corporate Communications
Tel.: +49 2461 61-1841
Email: e.zeiss@fz-juelich.de


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