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Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons
Published on: August 16, 2020
Dopamine quinones interact with alpha-synuclein to form unstructured adducts
Marco Bisaglia1, Laura Tosatto, Francesca Munari
1Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy.
Biochemical and Biophysical Research Communications
|March 16, 2010
Summary
Dopamine oxidation products (DAQ) may influence Parkinson's disease (PD) by interacting with alpha-synuclein (alphasyn). DAQ adducts with alphasyn retain an unfolded structure, suggesting non-covalent interactions are key, not stabilization of toxic protofibrils.
Area of Science:
- Neuroscience
- Biochemistry
- Structural Biology
Background:
- Alpha-synuclein (alphasyn) fibril formation is central to Parkinson's disease (PD) pathogenesis.
- Prefibrillar oligomeric species, or protofibrils, are increasingly implicated as the primary neurotoxic agents in PD.
- Dopamine oxidation products (DAQ) are known to inhibit alphasyn fibril formation, potentially by stabilizing these protofibrils.
Purpose of the Study:
- To structurally characterize alpha-synuclein/DAQ adducts.
- To investigate the nature of modifications induced by DAQ on alpha-synuclein.
- To determine if DAQ stabilizes toxic alphasyn protofibrils.
Main Methods:
- Biochemical techniques
- Biophysical techniques
- Structural characterization of alphasyn/DAQ adducts
Main Results:
- Alpha-synuclein/DAQ adducts were isolated and structurally characterized.
- Contrary to protofibrils, alphasyn/DAQ adducts were found to retain an unfolded conformation.
- Only a small fraction of alphasyn exhibited covalent interaction with DAQ; non-covalent interactions were predominant.
Conclusions:
- Dopamine oxidation products (DAQ) do not appear to stabilize alpha-synuclein (alphasyn) protofibrils.
- The primary interaction between DAQ and alphasyn involves non-covalent modifications, leading to an unfolded conformation.
- These findings suggest a different mechanism for DAQ's influence on alphasyn aggregation in Parkinson's disease pathogenesis.
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