Mutant Alpha-Synuclein Affects Microglial Behavior
Author Information
Author(s): Lalida Rojanathammanee, Eric J. Murphy, Colin K. Combs
Primary Institution: University of North Dakota School of Medicine and Health Sciences
Hypothesis
Expression of mutant forms of alpha-synuclein may contribute to the reactive microgliosis characteristic of Parkinson's disease brains.
Conclusion
Over-expression of alpha-synuclein drives microglial cells into a reactive phenotype with increased cytokine secretion and impaired phagocytic ability.
Supporting Evidence
- Over-expression of alpha-synuclein increased Cox-2 levels in BV2 cells.
- Transfected cells showed impaired phagocytic ability correlating with decreased LAMP-1 levels.
- Secretion of proinflammatory cytokines TNF-α and IL-6 was significantly higher in cells over-expressing alpha-synuclein.
Takeaway
When certain forms of a protein called alpha-synuclein are over-expressed in brain cells, it makes them act differently, causing them to release more chemicals that can lead to inflammation but also makes them worse at cleaning up debris.
Methodology
Murine microglial cell line BV2 was transfected to express human wild type and mutant alpha-synuclein, and changes in microglial phenotype were assessed using Western blot analysis, ELISA, phagocytosis, and neurotoxicity assays.
Limitations
The study was conducted using a microglial cell line, which may not fully represent primary microglial behavior.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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