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 Nano-Saturn
14.06.2018 | Gesellschaft Deutscher Chemiker e.V.

nachricht Überlistetes Immunsystem schützt vor Herzinfarkt und Schlaganfall
14.06.2018 | Universität Duisburg-Essen

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: Li-Fi erstmals für das industrielle Internet der Dinge getestet

Mit einer Abschlusspräsentation im BMW Werk München wurde das BMBF-geförderte Projekt OWICELLS erfolgreich abgeschlossen. Dabei wurde eine Li-Fi Kommunikation zu einem mobilen Roboter in einer 5x5m² Fertigungszelle demonstriert, der produktionsübliche Vorgänge durchführt (Teile schweißen, umlegen und prüfen). Die robuste, optische Drahtlosübertragung beruht auf räumlicher Diversität, d.h. Daten werden von mehreren LEDs und mehreren Photodioden gleichzeitig gesendet und empfangen. Das System kann Daten mit mehr als 100 Mbit/s und fünf Millisekunden Latenz übertragen.

Moderne Produktionstechniken in der Automobilindustrie müssen flexibler werden, um sich an individuelle Kundenwünsche anpassen zu können. Forscher untersuchen...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: ALMA entdeckt Trio von Baby-Planeten rund um neugeborenen Stern

Neuartige Technik, um die jüngsten Planeten in unserer Galaxis zu finden

Zwei unabhängige Astronomenteams haben mit ALMA überzeugende Belege dafür gefunden, dass sich drei junge Planeten im Orbit um den Säuglingsstern HD 163296...

Im Focus: Robotik live auf der automatica – Fraunhofer IPK führt Automatisierungslösungen vor

Auf der diesjährigen automatica in München präsentiert das Fraunhofer IPK zwei Technologie-Innovationen aus dem Bereich Robotik „in Aktion“: Ein Agrar-Roboter für die Ernte von Einlegegurken sowie eine Oberkörper-Softorthese zur Unterstützung von Industrie-Arbeitskräften werden erstmals live auf einer Messe vorgeführt.

Roboter für die Gurkenernte

Im Focus: Neutrinos auf der genauesten Waage der Welt

Wie schwer sind Neutrinos? Diese unscheinbare Frage gehört zu den wichtigsten Fragestellungen in der modernen Teilchenphysik und Kosmologie. Der Antwort einen großen Schritt näher bringt uns das Karlsruher Tritium Neutrino Experiment KATRIN. Es wurde am Karlsruher Institut für Technologie von einer internationalen Kollaboration in 15-jähriger Bauzeit aufgebaut und beginnt am 11. Juni 2018 mit einer feierlichen Eröffnung seine mehrjährige Messphase.

Die Neutrinowaage KATRIN nimmt den Messbetrieb auf. Nach Hauptspektrometer und Detektoreinheit ist mit der Tritiumquelle auch die letzte der Großkomponenten...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

VideoLinks
Industrie & Wirtschaft
Veranstaltungen

Internationale Konferenz zur Asteroidenforschung in Garching

13.06.2018 | Veranstaltungen

Meteoriteneinschläge und Spektralfarben: HITS bei Explore Science 2018

11.06.2018 | Veranstaltungen

Zweite International Baltic Earth Conference in Dänemark: “The Baltic Sea region in Transition”

08.06.2018 | Veranstaltungen

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

Fußball durch die Augen des Computers

14.06.2018 | Informationstechnologie

Massenverlust des Antarktischen Eisschilds hat sich beschleunigt

14.06.2018 | Studien Analysen

Quanten-Übertragung auf Knopfdruck

14.06.2018 | Physik Astronomie

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