idw – Informationsdienst Wissenschaft

Nachrichten, Termine, Experten

Grafik: idw-Logo
idw-Abo
Medienpartner:
Wissenschaftsjahr


Share on: 
09/03/2019 08:00

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

Dr.rer.nat. Arne Claussen Stabsstelle Presse und Kommunikation
Heinrich-Heine-Universität Düsseldorf

    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. 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.”


    Original publication:

    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


    More information:

    https://elifesciences.org/articles/46112


    Criteria of this press release:
    Journalists, Scientists and scholars
    Biology, Chemistry, Medicine
    transregional, national
    Research results, Scientific Publications
    English


    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)


    For download

    x

    Help

    Search / advanced search of the idw archives
    Combination of search terms

    You can combine search terms with and, or and/or not, e.g. Philo not logy.

    Brackets

    You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).

    Phrases

    Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.

    Selection criteria

    You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).

    If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).

    Cookies optimize the use of our services. By surfing on idw-online.de you agree to the use of cookies. Data Confidentiality Statement
    Okay