Aug 24, 2007

Different species of alpha-synuclein oligomers induce calcium influx and seeding

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Karin M DanzerMarcus Kostka

Abstract

Aggregation of alpha-synuclein (alpha-syn) has been linked to the pathogenesis of Parkinson's disease (PD) and other neurodegenerative diseases. Increasing evidence suggests that prefibrillar oligomers and protofibrils, rather than mature fibrils of alpha-syn, are the pathogenic species in PD. Despite extensive effort on studying oligomerization of alpha-syn, no studies have compared different oligomer species directly on a single-particle level and investigated their biological effects on cells. In this study, we applied a novel highly sensitive single molecule detection system that allowed a direct comparison of different oligomer types. Furthermore, we studied biological effects of different oligomer types on cells. For this purpose, we developed new oligomerization protocols, that enabled the use of these different oligomers in cell culture. We found that all of our three aggregation protocols resulted in heterogeneous populations of oligomers. Some types of oligomers induced cell death via disruption of cellular ion homeostasis by a presumably pore-forming mechanism. Other oligomer types could directly enter the cell resulting in increased alpha-syn aggregation. Based on our results, we propose that under various physiolog...Continue Reading

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Mentioned in this Paper

Pathogenic Aspects
SNCA gene
Calcium [EPC]
Transfection
Pathogenesis
Cell Injury
Calcium
Pathogenic Organism
Proteins, Recombinant DNA
Resting Potentials

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