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Published on: August 13, 2017
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Ca2+ -Calmodulin-Calcineurin Signaling Modulates α-Synuclein Transmission
Jun Ueda1, Norihito Uemura1, Tomoyuki Ishimoto1
1Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Summary
Calcium signaling pathways influence alpha-synuclein transmission in Parkinson's disease. Inhibiting calcineurin reduces alpha-synuclein pathology, suggesting a potential therapeutic target.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Intercellular transmission of pathogenic proteins like alpha-synuclein drives neurodegenerative diseases.
- Neuronal uptake of these proteins is activity-dependent, but mechanisms in Parkinson's disease are not fully understood.
Purpose of the Study:
- To investigate the role of calcium (Ca2+) -calmodulin-calcineurin signaling in alpha-synuclein transmission.
- To explore this signaling pathway as a potential therapeutic target for Parkinson's disease.
Main Methods:
- Utilized mouse primary hippocampal neurons to study alpha-synuclein preformed fibril uptake.
- Examined the impact of modulating Ca2+-calmodulin-calcineurin signaling on pathology development in a mouse model of Parkinson's disease.
Main Results:
- Inhibition of Ca2+ channels, calmodulin, and calcineurin blocked alpha-synuclein uptake via macropinocytosis.
- Different voltage-gated Ca2+ channel subtypes showed varied contributions to alpha-synuclein uptake.
- Calcineurin inhibition ameliorated alpha-synuclein pathology in inoculated wild-type mice.
Conclusions:
- Ca2+-calmodulin-calcineurin signaling significantly modulates alpha-synuclein transmission.
- This signaling pathway represents a promising therapeutic target for Parkinson's disease treatment.
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