Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research into Parkinson’s disease: binding-protein prevents fibril proliferation

03.09.2019

Physical biology: publication in eLife

Several neurodegenerative diseases such as Parkinson’s are closely linked to the aggregation of a specific protein, α-synuclein. An international collaborative project involving Heinrich Heine University Düsseldorf (HHU), Forschungszentrum Jülich (FZJ) and RWTH Aachen University has now shed light on the mechanisms used by a specific binding-protein discovered by them to prevent aggregation.


Aggregation inhibitor beta-wrapin AS69 (grey) binds a region in the otherwise disordered Parkinson’s protein alpha-synuclein (orange), preventing elongation and formation of new protein fibrils (red).

HHU / Wolfgang Hoyer

In the journal eLife, they also describe how the binding-protein improves symptoms of Parkinson’s disease in fruit flies.

Protein aggregates have been observed in the nerve tissue of patients with Parkinson’s disease which consist of individual components (monomers) of the protein α-synuclein which assemble into what are referred to as amyloid fibrils.

Similar deposits are also found in the case of other neurodegenerative diseases such as Alzheimer’s. Researchers are looking for approaches to prevent fibril formation and potentially cure the diseases.

In 2014, Düsseldorf-based researchers led by Prof. Dr. Wolfgang Hoyer described how a class of engineered binding-proteins, β-wrapins, are able to prevent α-synuclein aggregation.

Hoyer says: “We subsequently investigated with research partners precisely how the β-wrapins function and where they disrupt the α-synuclein aggregation process.”

The collaborative group including first author of the study Emil D. Agerschou and Prof. Hoyer from the Chair of Physical Biology at HHU and the FZJ, Prof. Dr. Alexander Büll (Technical University of Denmark) and Prof. Dr. Björn Falkenburger (Technical University of Dresden) as well as other partners at the University of Cambridge and the German Center for Neurodegenerative Diseases in Bonn has now presented its findings in the journal eLife.

Firstly, the researchers found out that the β-wrapins prevent new α-synuclein monomers from elongating the amyloid fibrils. To do this, the β-wrapins capture the monomers and form chemical complexes with them.

But there is a further property that makes the β-wrapins particularly effective, as explained by Emil Agerschou: “The β-wrapins prevent seed fibrils from forming in the first place. It is especially relevant that very small amounts of the wrapins are sufficient for this to happen, so you don’t need a binding-protein for every monomer.”

This is referred to as a ‘sub-stoichiometric effect’ that makes the process especially effective. It is the aforementioned complexes comprising binding-proteins and monomers that are responsible for inhibiting seed formation.

“We discovered a few years ago that α-synuclein fibrils can proliferate quickly under certain conditions in a kind of chain reaction. We were really astonished to see that the β-wrapins suppress the chain reactions very efficiently”, adds Prof. Büll: “We think we now understand how this is achieved.”

In addition, the researchers have examined the effect of the β-wrapins not only in test tubes but also in cell culture and in animal models. Diseased fruit flies (Drosophila) treated with β-wrapins displayed notably improved motor skills in a climbing assay.

Prof. Hoyer is still cautious about potential therapeutic use: “The positive results in living creatures give us hope that we have possibly found a path to an active ingredient through the β-wrapins. However, it will still be a long time before this could potentially be used for humans.”

Originalpublikation:

E. D. Agerschou, T. Saridaki, P. Flagmeier, C. Galvagnion, D. Komnig, L. Heid, V. Prasad, H. Shaykhalishahi, D. Willbold, C. M. Dobson, A. Voigt, B. H. Falkenburger, W. Hoyer, A. K. Buell, An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils, eLife 2019;8:e46112
DOI: 10.7554/eLife.46112

Weitere Informationen:

https://elifesciences.org/articles/46112

HHU Dr.rer.nat. Arne Claussen | idw - Informationsdienst Wissenschaft
Further information:
http://www.hhu.de/

More articles from Life Sciences:

nachricht Blue Brain finds how neurons in the mouse neocortex form billions of synaptic connections
02.09.2019 | Ecole Polytechnique Fédérale de Lausanne

nachricht Unique fingerprint: What makes nerve cells unmistakable?
02.09.2019 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Next generation video: WDR and Fraunhofer HHI present significantly improved video quality at IFA 2019

The demand for even higher resolution videos will continue to increase in the coming years. For this reason, the German public service broadcaster WDR and the Fraunhofer Heinrich Hertz Institute HHI will collaborate in the coming months to test the Video Coding possibilities offered by the next international standard VVC/H.266.

VVC/H.266 is the successor standard to HEVC/H.265. The latter is currently the most modern and efficient standard for Video Coding and is used, for example, in...

Im Focus: Nanodiamonds in the brain

The recording of images of the human brain and its therapy in neurodegenerative diseases is still a major challenge in current medical research. The so-called blood-brain barrier, a kind of filter system of the body between the blood system and the central nervous system, constrains the supply of drugs or contrast media that would allow therapy and image acquisition. Scientists at the Max Planck Institute for Polymer Research (MPI-P) have now produced tiny diamonds, so-called "nanodiamonds", which could serve as a platform for both the therapy and diagnosis of brain diseases.

The blood-brain barrier is a physiological boundary layer that works highly selectively and thus protects the brain: On the one hand, pathogens or toxins are...

Im Focus: Entanglement sent over 50 km of optical fiber

For the first time, a team led by Innsbruck physicist Ben Lanyon has sent a light particle entangled with matter over 50 km of optical fiber. This paves the way for the practical use of quantum networks and sets a milestone for a future quantum internet.

The quantum internet promises absolutely tap-proof communication and powerful distributed sensor networks for new science and technology. However, because...

Im Focus: Hamburg and Kiel researchers observe spontaneous occurrence of skyrmions in atomically thin cobalt films

Since their experimental discovery, magnetic skyrmions - tiny magnetic knots - have moved into the focus of research. Scientists from Hamburg and Kiel have now been able to show that individual magnetic skyrmions with a diameter of only a few nanometres can be stabilised in magnetic metal films even without an external magnetic field. They report on their discovery in the journal Nature Communications.

The existence of magnetic skyrmions as particle-like objects was predicted 30 years ago by theoretical physicists, but could only be proven experimentally in...

Im Focus: Physicists create world's smallest engine

Theoretical physicists at Trinity College Dublin are among an international collaboration that has built the world's smallest engine - which, as a single calcium ion, is approximately ten billion times smaller than a car engine.

Work performed by Professor John Goold's QuSys group in Trinity's School of Physics describes the science behind this tiny motor.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

AI for Laser Technology Conference: optimizing the use of lasers with artificial intelligence

29.08.2019 | Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

 
Latest News

Research into Parkinson’s disease: binding-protein prevents fibril proliferation

03.09.2019 | Life Sciences

Oldest European lake reveals its secrets

03.09.2019 | Earth Sciences

Next generation video: WDR and Fraunhofer HHI present significantly improved video quality at IFA 2019

03.09.2019 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>