Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Parkinson's disease: iron accumulation to the point of demise

19.08.2009
RUB scientists prove the iron-containing protein complex ferritin in cerebral neurons

Possible explanation for the necrosis of dopaminergic cells

Neurons that produce the neurotransmitter dopamine are the cerebral cells that most commonly die-off in Parkinson's disease. The cells in the so-called substantia nigra, which contain the dark pigment neuromelanin, are affected. It is also known that the iron content of these cells increases during the course of Parkinson's disease.

A team of researchers from the University of Bochum working under the auspices of Prof. Katrin Marcus and in close collaboration with colleagues in Munich and Würzburg studied this process in greater depth.

They have managed to make a first-time decisive observation, namely to provide evidence of ferritin in the neuromelanin granules in the affected brain cells. Ferritin is an iron depot protein that had only been proven in the supporting cells of the brain to date, but not in neurons. The scientists have published their results in Molecular & Cellular Proteomics.

Dark cerebral matter fades in Parkinson's disease

Investigation of the human brain discloses a distinct dark discoloration of the substantia nigra and locus coeruleus within parts of the brainstem. This is due to the bluish to brown-black pigment neuromelanin, which is only present in the human brain and that of a few other mammals (primates, cows, horses, some breeds of sheep). Research into neuromelanin is particularly interesting because the substantia nigra of patients with PD fades in colour during the course of the disease. The pigment is most common in dopaminergic neurons, which mostly die-off in PD patients. Dopamine is an important neurotransmitter. Motor control is impaired if dopaminergic cells decay. This in turn results in the symptoms typical of Parkinson's disease such as resting tremor, increasing postural instability and poor coordination of general movements.

Protective effect due to the "interception" of iron

After the researchers from Bochum and Würzburg had been able to clarify the composition and production of the neuromelanin granules four years ago, they began investigating the inner life of neuromelanin granules in greater detail. The significance of the currently obtained data is that the selective necrosis of the dopaminergic neurons in the substantia nigra is accompanied by an accumulation of ferrous ions (Fe3+). The homeostasis of the iron content is evidently damaged and this intensifies as the disease progresses. Elevated quantities of free Fe3+ result - inter alia - in an increased formation of cell-damaging free radicals which ultimately leads to necrosis of the cells. Neuromelanin is capable of bonding ferrous ions (and other heavy metals). For many decades, it had been uncertain whether the cells are protected by the pigment "intercepting" ferrous ions, or whether the accumulation of the iron was actually responsible for damaging the cells. Data gained during the past few years indicates that neuromelanin primarily plays a protective role for the neurons.

Additional iron accumulation mechanism

During the current study, the scientists thus investigated whether there could be a further mechanism for the accumulation of iron in the substantia nigra over and above the direct binding of the Fe3+ to neuromelanin. For the first time, they were now able to supply evidence of ferritin in the neuromelanin granules using a combination of diverse techniques (one-dimensional SDS gel electrophoresis, targeted mass spectrometry, western blot analysis, as well as immune transmission electron microscopy). To date, this important iron depot protein had only been proven in glia but not in neurons.

New hypothesis on the development of Parkinson's disease

Prof. Katrin Marcus concludes that - in the opinion of her research team - ferritin in the neuromelanin granules is a further significant element in the homeostasis of the iron content in the substantia nigra. This first direct proof of ferritin in neuromelanin granules in dopaminergic neurons is an important step towards an improvement in the comprehension of the iron metabolism in the human substantia nigra. It moreover supplies arguments for new hypotheses concerning the mechanisms of the iron-regulated degeneration of the substantia nigra in Parkinson's disease. Currently the scientists are investigating further unclarified issues, such as how the composition of the neuromelanin granules changes with increasing age and during the course of the disease. Moreover, they are trying to elucidate the exact function of the neuromelanin in the cell, and why only the neuromelanin-containing cells in the substantia nigra die-off.

Cooperation partners and sponsors

The research work performed by Prof. Katrin Marcus, Prof. Helmut E. Meyer, Dr. Florian Tribl and Dr. Elmar Langenfeld from the Medizinisches Proteom-Center at the Ruhr University Bochum in collaboration with the Julius-Maximilian University Würzburg (Prof. Manfred Gerlach, Prof. Peter Riederer, Prof. Esther Asan, Prof. Thomas Tatschner, Prof. Gerhard Bringmann) and the Ludwig-Maximilian University Munich (Dr. Thomas Arzberger) is sponsored by the Austrian Science Academy, BrainNet Europe, the German Parkinson Association and the German Federal Ministry of Education and Research (BMBF, Programs NGFN2 and NGFNplus).

Title

Tribl F, Asan E, Arzberger T, Tatschner T, Langenfeld E, Meyer HE, Bringmann G, Riederer P, Gerlach M, Marcus K. Identification of L-ferritin in neuromelanin granules of the human substantia nigra - a targeted proteomics approach. Mol Cell Proteomics 2009; 8:1832-38, doi:10.1074/mcp.M900006-MCP200

Publication 2005: Tribl F, Gerlach M, Marcus K, Asan E, Tatschner T, Arzberger T, Meyer HE, Bringmann G, Riederer P. "Subcellular proteomics" of neuromelanin granules isolated from the human brain. Mol Cell Proteomics. 2005;4(7):945-57

Further Information

Prof. Katrin Marcus, Department of Functional Proteomics, Medical Proteomic Center at the Ruhr-University Bochum, MA 4/59a, 44780 Bochum, -Tel. 0234/32-28444, Fax: 0234/32-14554, E-Mail: katrin.marcus@rub.de

Editor: Meike Drießen

Dr. Josef König | idw
Further information:
http://www.ruhr-uni-bochum.de/

More articles from Life Sciences:

nachricht Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>