The present address of Karin M. Danzer is the MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Seeding induced by α-synuclein oligomers provides evidence for spreading of α-synuclein pathology
Article first published online: 4 AUG 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 111, Issue 1, pages 192–203, October 2009
How to Cite
Danzer, K. M., Krebs, S. K., Wolff, M., Birk, G. and Hengerer, B. (2009), Seeding induced by α-synuclein oligomers provides evidence for spreading of α-synuclein pathology. Journal of Neurochemistry, 111: 192–203. doi: 10.1111/j.1471-4159.2009.06324.x
- Issue published online: 14 SEP 2009
- Article first published online: 4 AUG 2009
- Received July 18, 2009; accepted July 28, 2009.
- Parkinson’s disease;
Lewy bodies, α-synuclein (α-syn) immunopositive intracellular deposits, are the pathological hallmark of Parkinson’s disease (PD). Interestingly, Lewybody-like structures have been identified in fetal tissue grafts about one decade after transplantation into the striatum of PD patients. One possible explanation for the accelerated deposition of α-syn in the graft is that the aggregation of α-syn from the host tissue to the graft is spread by a prion disease-like mechanism. We discuss here an in vitro model which might recapitulate some aspects of disease propagation in PD. We found here that in vitro-generated α-syn oligomers induce transmembrane seeding of α-syn aggregation in a dose- and time-dependent manner. This effect was observed in primary neuronal cultures as well as in neuronal cell lines. The seeding oligomers were characterized by a distinctive lithium dodecyl sulfate-stable oligomer pattern and could be generated in a dynamic process out of pore-forming oligomers. We propose that α-syn oligomers form as a dynamic mixture of oligomer types with different properties and that α-syn oligomers can be converted into different types depending on the brain milieu conditions. Our data indicate that extracellular α-syn oligomers can induce intracellular α-syn aggregation, therefore we hypothesize that a similar mechanism might lead to α-syn pathology propagation.