An international team of researchers, including Dr. Wilma van de Berg from Amsterdam UMC | Amsterdam Neuroscience and Prof. Henning Stahlberg from the Biozentrum, University of Basel, challenges the conventional understanding of the cause of Parkinson’s disease. The researchers have shown that the plaques in the brain’s neurons, characteristic of Parkinson‘s disease, are comprised of a membranous medley rather than protein fibrils. The recently published study in “Nature Neuroscience” raises new questions about the development of Parkinson’s disease.
For decades, it was assumed that Parkinson’s disease is caused by deposits of insoluble protein fibrils in the Lewy bodies. In their current study, the Dutch, German and Swiss researchers refute this long held common thesis. Using state-of-the-art electron microscopes, they have been able to show that the Lewy bodies contain mainly membrane fragments, lipids and other cell debris instead of the anticipated alpha-synuclein fibrils.
“We used correlative light and electron microscopy to take a closer look at the postmortem substantia nigra of patients with Parkinson’s disease and discovered that the Lewy bodies consist mainly of membrane fragments from mitochondria and other organelles, but have in most cases no or only negligible quantities of protein fibrils,” say Van de Berg and Stahlberg. “This discovery was unexpected for us and the entire research field. We identified these plaques by their high concentration of the protein alpha-synuclein, but this is obviously not present in the form of fibrils.”
Currently, the researchers do not know yet where and in what form the protein alpha-suynuclein is hidden amongst the membrane fragments and how it is involved to plaque formation. However, their work indicates that the model of alpha-synuclein fibrils as a cause and mechanism of certain forms of Parkinson’s disease should be questioned. “It seems that the search for the origin of the disease has often chased the wrong target,” explain Van de Berg and Stahlberg. With their work, the researchers raise many new questions regarding the role of the plaques in the development of Parkinson’s disease. The insights into such cell structures also provide important clues for preventing the formation and spreading of plaques in the brain.
Sarah H. Shahmoradian, Amanda J. Lewis, Christel Genoud, Alexandra Graff-Meyer, Juergen Hench, Tim Moors, Gabriel Schweighauser, Jing Wang, Kenneth N. Goldie, Rosmarie Suetterlin, Daniel Castano-Diez, Paula Perez-Navarro, Evelien Huisman, Sabine Ipsen, Angela Ingrassia, Yvonne de Gier, Annemieke J.M.Rozemuller, Anne Da Paepe, Johannes Erny, Andreas Staempfli, Joerg Hoernschemeyer, FrederikGrosserueschkamp, Daniel Niedieker, Samir F. El-Mashtoly, Marialuida Quadri, Wilfred F.J. van IJcken, Vincenzo Bonifati, Klaus Gerwert, Bernd Bohrmann, Stephan Frank, Markus Britschgi, Henning Stahlberg, , Matthias E. Lauer. Lewy pathology in Parkinson's disease consists of crowded organelles and lipid membranes. Nature Neuroscience, published online 24 June 2019.
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