Alpha-synuclein potentiates Ca2+ influx through voltage-dependent Ca2+ channels
- 18 December 2006
- journal article
- Published by Wolters Kluwer Health in NeuroReport
- Vol. 17 (18) , 1883-1886
- https://doi.org/10.1097/wnr.0b013e3280115185
Abstract
Alpha-synuclein localized in synaptic terminals plays an important role in the pathogenesis of neurodegenerative diseases. The central domain of the protein, the nonamyloid component, is probably responsible for alpha-synuclein toxicity. Here, we report that alpha-synuclein and its nonamyloid component induced Ca2+ influx in rat synaptoneurosomes. The effect of alpha-synuclein was eliminated by the N-type specific Ca2+ channel blocker, omega-conotoxin GVIA. The antioxidant, resveratrol, and the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine, did not prevent alpha-synuclein-induced Ca2+ influx. Our findings indicate that alpha-synuclein stimulated Ca2+ influx through N-type voltage-dependent Ca2+ channels by a mechanism other than free radicals. A direct interaction between alpha-synuclein and N-type Ca2+ channels could be responsible for their effects on Ca2+ influx through voltage-dependent Ca2+ channels.Keywords
This publication has 19 references indexed in Scilit:
- Interaction between Aβ Peptide and α Synuclein: Molecular Mechanisms in Overlapping Pathology of Alzheimer’s and Parkinson’s in Dementia with Lewy Body DiseaseNeurochemical Research, 2006
- α-Synuclein and its neurotoxic fragment inhibit dopamine uptake into rat striatal synaptosomesNeurochemistry International, 2006
- Proteolytic Cleavage of Extracellular Secreted α-Synuclein via Matrix MetalloproteinasesJournal of Biological Chemistry, 2005
- Intraneuronal amyloid‐β1‐42 production triggered by sustained increase of cytosolic calcium concentration induces neuronal deathJournal of Neurochemistry, 2004
- Recent Advances on α-Synuclein Cell Biology: Functions and DysfunctionsCurrent Molecular Medicine, 2003
- Alzheimer's β-Amyloid, Human Islet Amylin, and Prion Protein Fragment Evoke Intracellular Free Calcium Elevations by a Common Mechanism in a Hypothalamic GnRH Neuronal Cell LineJournal of Biological Chemistry, 2000
- Toxicity of non‐Aβ component of Alzheimer's disease amyloid, and N‐terminal fragments thereof, correlates to formation of β‐sheet structure and fibrilsEuropean Journal of Biochemistry, 2000
- Widespread Alterations of α-Synuclein in Multiple System AtrophyThe American Journal of Pathology, 1999
- Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α‐synucleinAnnals of Neurology, 1998
- Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminalJournal of Neuroscience, 1988