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Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
Published on: June 26, 2018
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Alpha-synuclein activates the classical complement pathway and mediates complement-dependent cell toxicity
Emil Gregersen1,2, Cristine Betzer1,2, Woojin S Kim3
1DANDRITE, The Danish Research Institute of Translational Neuroscience, Aarhus University, Aarhus C, Denmark.
Journal of Neuroinflammation
|August 17, 2021
Summary
Alpha-synuclein activates the complement system, causing cell damage in synucleinopathies like Parkinson's disease. Complement inhibitors reduced this toxicity, suggesting a pro-neurodegenerative role for the complement system.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Synucleinopathies involve neurodegeneration and alpha-synuclein aggregation.
- The complement system, involved in CNS functions, mediates synapse loss in Alzheimer's disease.
- The role of the complement system in alpha-synuclein-associated diseases remains unclear.
Purpose of the Study:
- Investigate the complement system's pathological role in synucleinopathies.
- Assess complement-mediated effects on alpha-synuclein expressing cells.
- Examine direct complement activation by alpha-synuclein.
Main Methods:
- Assessed complement system effects on alpha-synuclein expressing cell viability.
- Examined direct complement activation by alpha-synuclein using a plate-based assay.
- Measured C1q levels in postmortem brain samples from multiple system atrophy (MSA) patients.
Main Results:
- Alpha-synuclein activates the classical complement pathway.
- Complement-dependent toxicity in alpha-synuclein expressing cells was demonstrated.
- Complement inhibitors (RaCI, Cp20) rescued alpha-synuclein-induced cellular toxicity.
- A trend towards higher C1q levels in MSA brains was observed.
Conclusions:
- Alpha-synuclein activates the classical complement pathway.
- The complement system contributes to alpha-synuclein-dependent cytotoxicity.
- The complement system may play a pro-neurodegenerative role in synucleinopathies.
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