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12:01
Detection of Disease-associated α-synuclein by Enhanced ELISA in the Brain of Transgenic Mice Overexpressing Human A53T Mutated α-synuclein
Published on: May 30, 2015
Parkinson's disease-associated alpha-synuclein is a calmodulin substrate
Jessica Martinez1, Ines Moeller, Hediye Erdjument-Bromage
1Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
The Journal of Biological Chemistry
|March 1, 2003
Summary
Calmodulin (CaM) interacts with alpha-synuclein, a protein linked to Parkinson's disease (PD). This interaction, dependent on calcium, influences alpha-synuclein's structure and fibril formation, potentially explaining calcium's role in PD pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Alpha-synuclein is central to Parkinson's disease (PD) pathogenesis, forming Lewy bodies.
- Mutations in alpha-synuclein cause autosomal dominant PD.
- The physiological role of alpha-synuclein, a synaptic protein, remains unclear.
Purpose of the Study:
- To identify novel synuclein-interacting proteins.
- To clarify the physiology of alpha-synuclein.
- To identify factors regulating alpha-synuclein conformation.
Main Methods:
- Incorporation of photoprobes into synuclein.
- Purification and identification of cross-linked proteins.
- In vitro and in-cell interaction studies.
Main Results:
- Calmodulin (CaM) was identified as a synuclein-interacting protein.
- CaM binds alpha-synuclein (wild type and mutants) in a calcium-dependent manner.
- Activated CaM accelerates alpha-synuclein fibril formation in vitro.
Conclusions:
- CaM interaction mediates calcium's control over synuclein function.
- CaM may alter alpha-synuclein conformation.
- This interaction provides insights into PD pathogenesis.
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