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Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
Polyunsaturated fatty acids induce alpha-synuclein-related pathogenic changes in neuronal cells
Karen Assayag1, Evgenia Yakunin, Virginie Loeb
1Department of Cellular Biochemistry and Human Genetics, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
The American Journal of Pathology
|December 7, 2007
Summary
Polyunsaturated fatty acids (PUFAs) promote alpha-synuclein (alphaS) aggregation in dopaminergic cells, forming toxic oligomers that precede Lewy-like inclusions. These inclusions may offer cellular protection against neurodegeneration in Parkinson's disease.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Misfolding and aggregation of alpha-synuclein (alphaS) are central to Parkinson's disease (PD) and dementia with Lewy bodies (DLB).
- Alpha-synuclein aggregates into Lewy bodies and Lewy neurites in affected neurons.
- Lipid interactions with alphaS are increasingly recognized as significant.
Purpose of the Study:
- To investigate the role of alpha-synuclein-polyunsaturated fatty acid (PUFA) interactions in Parkinson's disease-like pathology.
- To determine if PUFA exposure can induce alphaS aggregation and inclusions in neuronal cells.
- To assess the cytotoxicity of alphaS oligomers versus inclusions.
Main Methods:
- Overexpression of alphaS in dopaminergic and neuronal cell lines.
- Treatment of cells with physiological levels of PUFAs.
- Kinetic analysis of alphaS aggregation and inclusion formation.
- Assessment of cellular toxicity.
Main Results:
- Exposure to PUFAs induced the formation of proteinaceous inclusions in alphaS-overexpressing cells.
- Soluble alphaS oligomers, induced by PUFAs, were observed to precede the formation of these inclusions.
- AlphaS oligomers were cytotoxic, while the developed inclusions appeared protective.
Conclusions:
- Alterations in PUFA levels can drive alpha-synuclein aggregation.
- PUFA-induced alphaS oligomers are potentially cytotoxic and precede the formation of Lewy-like inclusions.
- Lewy-like inclusions may represent a protective cellular response to alphaS aggregation.
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