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Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays
Published on: August 13, 2017
Alpha-synuclein potentiates Ca2+ influx through voltage-dependent Ca2+ channels
Agata Adamczyk1, Joanna B Strosznajder
1Department of Cellular Signaling, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. agatazambrzycka@hotmail.com
Neuroreport
|December 21, 2006
Summary
Alpha-synuclein triggers calcium (Ca2+) influx via N-type channels in neurons. This suggests a direct interaction, potentially contributing to neurodegeneration, independent of free radicals.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Alpha-synuclein in synaptic terminals is implicated in neurodegenerative disease pathogenesis.
- The protein's central domain, the nonamyloid component, is a likely driver of alpha-synuclein toxicity.
Purpose of the Study:
- To investigate the effect of alpha-synuclein and its nonamyloid component on calcium influx in neuronal preparations.
- To elucidate the specific calcium channel subtypes and mechanisms involved in alpha-synuclein-induced calcium influx.
Main Methods:
- Experiments were conducted using rat synaptoneurosomes.
- Calcium influx was measured following exposure to alpha-synuclein and its nonamyloid component.
- The study utilized N-type specific calcium channel blockers (omega-conotoxin GVIA), an antioxidant (resveratrol), and a nitric oxide synthase inhibitor (Nomega-nitro-L-arginine) to probe the underlying mechanisms.
Main Results:
- Alpha-synuclein and its nonamyloid component induced significant Ca2+ influx in rat synaptoneurosomes.
- The N-type specific Ca2+ channel blocker, omega-conotoxin GVIA, completely abolished the effect of alpha-synuclein.
- Neither the antioxidant resveratrol nor the nitric oxide synthase inhibitor prevented alpha-synuclein-induced Ca2+ influx, suggesting a mechanism independent of free radicals and nitric oxide.
Conclusions:
- Alpha-synuclein stimulates Ca2+ influx through N-type voltage-dependent Ca2+ channels.
- The mechanism does not appear to involve free radicals or nitric oxide.
- A direct interaction between alpha-synuclein and N-type Ca2+ channels is proposed as the basis for the observed calcium influx.
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