Abstract |
Lewy bodies, alpha-synuclein (alpha-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 alpha-syn in the graft is that the aggregation of alpha-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 alpha-syn oligomers induce transmembrane seeding of alpha-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 alpha-syn oligomers form as a dynamic mixture of oligomer types with different properties and that alpha-syn oligomers can be converted into different types depending on the brain milieu conditions. Our data indicate that extracellular alpha-syn oligomers can induce intracellular alpha-syn aggregation, therefore we hypothesize that a similar mechanism might lead to alpha-syn pathology propagation.
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Authors | Karin M Danzer, Simon K Krebs, Michael Wolff, Gerald Birk, Bastian Hengerer |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 111
Issue 1
Pg. 192-203
(Oct 2009)
ISSN: 1471-4159 [Electronic] England |
PMID | 19686384
(Publication Type: Journal Article)
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Chemical References |
- Intermediate Filament Proteins
- Peptide Fragments
- desmuslin
- Calcium
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Topics |
- Animals
- Calcium
(metabolism)
- Cells, Cultured
- Cerebral Cortex
(cytology)
- Dose-Response Relationship, Drug
- Embryo, Mammalian
- Humans
- Intermediate Filament Proteins
(chemistry, genetics, metabolism, pharmacology)
- Mice
- Mutation
(genetics)
- Neuroblastoma
(pathology)
- Neurons
(drug effects, metabolism)
- Peptide Fragments
(chemistry, classification)
- Statistics, Nonparametric
- Time Factors
- Transfection
(methods)
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