How does Parkinson's disease develop? Study raises doubts on previous theory of Parkinson’s disease

Cross section of an alpha-synuclein fibril. Left: 3D reconstruction of the fibril, showing two interacting protein molecules. Right: atomic model of the fibril structure. University of Basel

The arms and legs tremble incessantly, the muscles become weaker and the movements slower − these are typical symptoms that many Parkinson's patients suffer from. More than six million people are affected worldwide. In these patients, the dopamine-producing nerve cells in the brain slowly die off. The resulting lack of this neurotransmitter impairs motor function and often also affects the cognitive abilities.

Questionable: protein fibrils cause Parkinson's disease

So far, it was assumed that the protein alpha-synuclein is one of the trigger factors. This protein can clump together and form small needles, so-called fibrils, which accumulate and deposit as Lewy bodies in the nerve cells. These toxic fibrils damage the affected brain cells.

A team of scientists led by Prof. Henning Stahlberg from the Biozentrum of the University of Basel, in collaboration with researchers from Hoffmann-La Roche Ltd. and the ETH Zurich, have now artificially generated an alpha-synuclein fibril in the test tube. They have been able to visualize for the first time its three-dimensional structure with atomic resolution. “Contrary to our expectations, the results seem to raise more questions than they can hope to answer,” says Stahlberg.

It is important to know that in some congenital forms of Parkinson's disease, affected persons carry genetic defects in the alpha-synuclein gene. These mutations, it is suspected, eventually cause the protein to fold incorrectly, thus forming dangerous fibrils.

“However, our 3D structure reveals that a mutated alpha-synuclein protein should not be able to form these type of fibrils,” says Stahlberg. “Because of their location, most of these mutations would rather hinder the formation of the fibril structure that we have found.” In brief, if the fibril structure causes Parkinson's disease, the genetic defect would have to protect against the disease. But this is not the case. So, it could be possible that a different type of fibril or another form of the protein triggers the disease in these patients.

Study poses new questions

More investigations are now needed to understand this fibril structure. What are the effects of the alpha-synuclein mutations? Do they lead to distinct forms of protein aggregates? What is the role of the fibrils for the nerve cells, and why do these cells die? To date, the exact physiological function of alpha-synuclein is still not known. Since only the symptoms of this neurodegenerative disease can be alleviated with the current medications, new concepts are urgently needed.

Original source

Ricardo Guerrero-Ferreira, Nicholas M.I. Taylor, Daniel Mona, Philippe Ringler, Matthias E. Lauer, Roland Riek, Markus Britschgi, and Henning Stahlberg.
Cryo-EM structure of alpha-synuclein fibrils
eLife, published online 3 July 2018, doi: 10.7554/eLife.36402

Further information

Prof. Dr. Henning Stahlberg, University of Basel, Biozentrum, Tel. +41 61 387 32 62, E-Mail: henning.stahlberg@unibas.ch

https://elifesciences.org/articles/36402 Original source

Media Contact

Christoph Dieffenbacher Universität Basel

Weitere Informationen:

http://www.unibas.ch

Alle Nachrichten aus der Kategorie: Life Sciences

Articles and reports from the Life Sciences area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Zurück zur Startseite

Kommentare (0)

Schreib Kommentar

Neueste Beiträge

How Stable is the Antarctic Ice Sheet?

Scientists from Heidelberg University investigate which factors determine the stability of ice masses in East Antarctica. As temperatures rise due to climate change, the melting of polar ice sheets is…

Smart sensors for future fast charging batteries

European project “Spartacus” launched Faster charging, longer stability of performance not only for electric vehicles but also for smartphones and other battery powered products. What still sounds like science fiction…

Small molecules control bacterial resistance to antibiotics

Antibiotics have revolutionized medicine by providing effective treatments for infectious diseases such as cholera. But the pathogens that cause disease are increasingly developing resistance to the antibiotics that are most…

Partners

By continuing to use the site, you agree to the use of cookies. more information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close