Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

Parkinson-Krankheit: Neue Erkenntnisse über ein reisendes Protein

05.01.2016

A laboratory study indicates that one of the main proteins involved in Parkinson’s disease pathology does not behave as a ‘prion’. Researchers led by Prof. Donato Di Monte report on this in the journal “BRAIN”.

In Parkinson’s disease, the protein “alpha-synuclein” aggregates within neurons of patients and appears to propagate across interconnected areas of the brain.


Für die aktuelle Studie schleusten DZNE-Forscher den Bauplan der menschlichen Variante von Alpha-Synuclein in die Nervenzellen (siehe gestrichelte Linie) von Mäusen. Quelle: DZNE/M. Helwig

How this happens remains largely unknown. It has been proposed that alpha-synuclein may behave like a “prion”: pathological forms of the protein may be capable of changing the conformation of normal alpha-synuclein and thus triggering its aggregation and neuron-to-neuron propagation (a phenomenon referred to as “seeding”).

Recent findings by scientists at the German Center for Neurodegenerative Diseases (DZNE) reveal that aggregation, spreading and pathology caused by alpha-synuclein do not necessarily involve prion-like seeding. Instead, they could be triggered by enhanced alpha-synuclein expression and trans-neuronal passage of monomeric and oligomeric forms of the protein. Researchers led by Prof. Donato Di Monte report on this in the journal “BRAIN”.

Abundant evidence underscores a critical role of the protein alpha-synuclein in the pathogenesis of Parkinson’s disease. In particular, alpha-synuclein is a major component of the intraneuronal inclusions, named Lewy bodies, that are progressively accumulated in the brains of patients with Parkinson’s disease.

Alpha-synuclein pathology often starts in a region of the lower brain called medulla oblongata from where it spreads upwardly toward midbrain and cortical areas. In the current study, sponsored in part by the Paul Foundation, DZNE researchers mimicked this phenomenon in mice. With the aid of a tailor-made viral vector, they transferred the blueprint of the human alpha-synuclein gene specifically into neurons in the mouse medulla oblongata. These cells then began producing and accumulating relatively large amounts of the exogenous (human) alpha-synuclein.

Long-distance protein transmission

Using specific antibodies that recognize human alpha-synuclein, Di Monte and his colleagues tracked the spreading of this protein throughout the mouse brain over a period of 6 to 12 weeks. They also compared spreading and pathology in normal mice, which expressed both exogenous (human) and endogenous alpha-synuclein, versus mutant mice lacking their endogenous protein.

In both groups of animals, increased expression of human alpha-synuclein resulted in its progressive diffusion from the medulla oblongata toward more rostral brain regions. This protein spreading involved at least one trans-synaptic jump and followed a stereotypical pattern consistent with diffusion via anatomically interconnected pathways. Furthermore, accumulation of the spreading protein within recipient neurons was accompanied by evidence of neuronal damage.

Unlike prions

A prion-like seeding mechanism would predict that spreading of alpha-synuclein should be facilitated by interactions between abnormal forms of the protein generated within donor neurons and “uncorrupted” alpha-synuclein expressed within recipient cells. “In other words,” says Di Monte “we were expecting less efficient protein transmission and less pronounced pathology in mutant mice lacking endogenous alpha-synuclein. We were also expecting spreading and pathology to be associated with the accumulation of amyloidogenic alpha-synuclein; these are forms of the protein capable of producing insoluble fibrous aggregates.”

Contrary to these predictions, spreading of alpha-synuclein was enhanced rather than being counteracted by ablation of the endogenous protein in mutant mice. Furthermore, trans-neuronal passage of non-fibrillar alpha-synuclein species was responsible for protein diffusion and triggered neuronal pathology. The researcher explains, “We believe that these findings bear a number of important implications for disease pathogenesis. Not only can we conclude that long-distance diffusion of alpha-synuclein does not necessarily require the generation of prion-like species. Our data also reveal that spreading and pathology can be triggered by simple overexpression of the protein and are mediated, at least initially, by monomeric and/or oligomeric alpha-synuclein.”

Moving forward with studies on a “moving” protein

The possibility that alpha-synuclein may behave like a prion has raised the speculation that, similar to some prion diseases (for example, Creutzfeldt-Jakob disease), cases of Parkinson’s disease may arise from exposure to contagious protein species. Di Monte stresses: “There is absolutely no indication that Parkinson’s could be a contagious disease. In fact, an important contribution of our new study is that it emphasizes how critical aspects of Parkinson’s disease pathogenesis, such as neuron-to-neuron alpha-synuclein transmission and protein aggregation, can be explained by mechanisms that are not prion-like.”

Di Monte and his colleagues at the DZNE intend to continue working on alpha-synuclein and are particularly interested in elucidating how alpha-synuclein could be targeted to slow down or halt the pathologic and clinical progression of the disease.

Original publication
„Brain propagation of transduced α-synuclein involves nonfibrillar protein species and is enhanced in α-synuclein null mice“, Michael Helwig, Michael Klinkenberg, Raffaella Rusconi, Ruth E. Musgrove, Nour K. Majbour, Omar M.A. El-Agnaf, Ayse Ulusoy and Donato A. Di Monte, BRAIN, DOI: 10.1093/brain/awv376

The German Center for Neurodegenerative Diseases (DZNE) investigates the causes of diseases of the nervous system and develops strategies for prevention, treatment and care. It is an institution within the Helmholtz Association of German Research Centres with nine sites across Germany (Berlin, Bonn, Dresden, Göttingen, Magdeburg, Munich, Rostock/Greifswald, Tübingen and Witten). The DZNE cooperates closely with universities, their clinics and other research facilities.
Web: www.dzne.de/en  | Twitter: @dzne_en | Facebook: www.dzne.de/facebook 

Weitere Informationen:

http://www.dzne.de/en/about-us/public-relations/meldungen/2016/press-release-no-...

Dr. Marcus Neitzert | idw - Informationsdienst Wissenschaft
Weitere Informationen:
http://www.dzne.de

Weitere Nachrichten aus der Kategorie Biowissenschaften Chemie:

nachricht Blasentang zeigt gekoppelte Reaktionen auf Umweltveränderungen
15.10.2019 | GEOMAR Helmholtz-Zentrum für Ozeanforschung Kiel

nachricht Nachweis erbracht: Genmutation in Chloridkanal löst Hyperaldosteronismus aus
15.10.2019 | Forschungsverbund Berlin e.V.

Alle Nachrichten aus der Kategorie: Biowissenschaften Chemie >>>

Die aktuellsten Pressemeldungen zum Suchbegriff Innovation >>>

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

Im Focus: Rätsel gelöst: Das Quantenleuchten dünner Schichten

Eine ganz spezielle Art von Licht wird von Wolfram-Diselenid-Schichten ausgesandt. Warum das so ist, war bisher unklar. An der TU Wien wurde nun eine Erklärung gefunden.

Es ist ein merkwürdiges Phänomen, das jahrelang niemand erklären konnte: Wenn man einer dünnen Schicht des Materials Wolfram-Diselenid Energie zuführt, dann...

Im Focus: Wie sich Reibung bei topologischen Isolatoren kontrollieren lässt

Topologische Isolatoren sind neuartige Materialien, die elektrischen Strom an der Oberfläche leiten, sich im Innern aber wie Isolatoren verhalten. Wie sie auf Reibung reagieren, haben Physiker der Universität Basel und der Technischen Universität Istanbul nun erstmals untersucht. Ihr Experiment zeigt, dass die durch Reibung erzeugt Wärme deutlich geringer ausfällt als in herkömmlichen Materialien. Dafür verantwortlich ist ein neuartiger Quantenmechanismus, berichten die Forscher in der Fachzeitschrift «Nature Materials».

Dank ihren einzigartigen elektrischen Eigenschaften versprechen topologische Isolatoren zahlreiche Neuerungen in der Elektronik- und Computerindustrie, aber...

Im Focus: An ultrafast glimpse of the photochemistry of the atmosphere

Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.

The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...

Im Focus: Shaping nanoparticles for improved quantum information technology

Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.

Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...

Im Focus: Neuer Werkstoff für den Bootsbau

Um die Entwicklung eines Leichtbaukonzepts für Sportboote und Yachten geht es in einem Forschungsprojekt der Technischen Hochschule Mittelhessen. Prof. Dr. Stephan Marzi vom Gießener Institut für Mechanik und Materialforschung arbeitet dabei mit dem Bootsbauer Krake Catamarane aus dem thüringischen Apolda zusammen. Internationale Kooperationspartner sind Prof. Anders Biel von der schwedischen Universität Karlstad und die Firma Lamera aus Göteborg. Den Projektbeitrag der THM fördert das Bundesministerium für Wirtschaft und Energie im Rahmen des Zentralen Innovationsprogramms Mittelstand mit 190.000 Euro.

Im modernen Bootsbau verwenden die Hersteller als Grundmaterial vorwiegend Duroplasten wie zum Beispiel glasfaserverstärkten Kunststoff. Das Material ist...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

VideoLinks
Industrie & Wirtschaft
Veranstaltungen

Digitalisierung trifft Energiewende

15.10.2019 | Veranstaltungen

Bauingenieure im Dialog 2019: Vorträge stellen spannende Projekte aus dem Spezialtiefbau vor

15.10.2019 | Veranstaltungen

DFG unterstützt Kongresse und Tagungen - Dezember 2019

14.10.2019 | Veranstaltungen

VideoLinks
Wissenschaft & Forschung
Weitere VideoLinks im Überblick >>>
 
Aktuelle Beiträge

Familienunternehmer setzen eher auf Evolution als auf Disruption

16.10.2019 | Wirtschaft Finanzen

Wie ein infizierter Knochen besser heilt

16.10.2019 | Förderungen Preise

Rätsel gelöst: Das Quantenleuchten dünner Schichten

15.10.2019 | Physik Astronomie

Weitere B2B-VideoLinks
IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics