Skip to ContentSkip to Navigation
Over onsNieuws en agendaNieuwsberichten

C. elegans paper by Tjakko van Ham published in PLoS Genetics

21 maart 2008

Parkinson's disease is the second most common brain disorder of the elderly. It is thought to be caused by environmental and genetic factors. However, little is known about the genes and processes involved. Pathologically, Parkinson's disease is recognized by inclusions in the brain that contain a disease-specific protein: alpha-synuclein. We created a small animal model (C. elegans) in which we could follow the formation of alpha-synuclein inclusions in living and aging animals. With a genome-wide RNAi screen we identified 80 genes whose expression influences inclusion formation. These genes include evolutionarily conserved regulators of longevity, suggesting a link between inclusion formation and the molecular mechanism of aging. Our results offer a refined understanding of how Parkinson's disease arises during aging and we identify processes and genes that may underlie an increased susceptibility for the disease, which is important for improving diagnostics and developing strategies for therapeutic intervention.

C. elegans Model Identifies Genetic Modifiers of α -Synuclein Inclusion Formation During Aging

Tjakko J. van Ham, Karen L. Thijssen, Rainer Breitling, Robert M. W. Hofstra, Ronald H. A. Plasterk, Ellen A. A. Nollen

Summary

Inclusions in the brain containing α -synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a C. elegans model that makes it possible to monitor, in living animals, the formation of α -synuclein inclusions. In worms of old age, inclusions contain aggregated α - synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in α -synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between α -synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other α -synuclein related disorders.

See full text

A response to this paper can be found at http://www.alzforum.org/new/detail.asp?id=1780

More information about the work on C. elegans being performed in the Genetics Department can be found here.

Laatst gewijzigd:04 juli 2014 21:10

Meer nieuws

  • 20 september 2018

    Koninklijke onderscheiding voor professor dr. Cisca Wijmenga

    Cisca Wijmenga, hoogleraar humane genetica aan de Faculteit Medische Wetenschappen/UMCG, kreeg woensdag 19 september uit handen van locoburgemeester Ton Schroor van de gemeente Groningen een koninklijke onderscheiding. Wijmenga is benoemd tot Ridder...

  • 10 september 2018

    ZonMW-subsidie voor studie naar niertransplantatie

    Onderzoekers van de sectie Nefrologie & Transplantatie van het UMCG hebben een subsidie van maar liefst 1,2 miljoen euro gekregen van Zon MW. De subsidie is voor een groot multicenter onderzoek bij patiënten ouder dan 65 jaar die een niertransplantatie...

  • 07 september 2018

    UMCG onderzoekt effect behandeling met virtual reality voor fantoompijn

    Het UMCG doet mee aan een groot internationaal onderzoek naar een nieuwe behandeling van fantoompijn. Bij deze behandeling krijgen patiënten trainingen met behulp van virtual reality en augmented reality.