P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein-induced ATP release in neuroblastoma SH-SY5Y cells

Purinergic Signalling
Anna WilkaniecAgata Adamczyk

Abstract

Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy bodies, Alzheimer's disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling-particularly, P2 family receptors-in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied. Therefore, in this study, we have investigated the effect of ASN on P2 purinergic receptors and ATP-dependent signaling. We used neuroblastoma SH-SY5Y cell line and rat synaptoneurosomes treated with exogenous soluble ASN. The experiments were performed using spectrofluorometric, radiochemical, and immunochemical methods. We found the following: (i) ASN-induced intracellular free calcium mobilization in neuronal cells and nerve endings depends on the activation of purinergic P2X7 receptors; (ii) activation of P2X7 receptors leads ...Continue Reading

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Citations

Jan 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alexei A SurguchevAndrei Surguchov
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Jun 4, 2020·International Journal of Molecular Sciences·Anna WilkaniecAgata Adamczyk
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Jun 26, 2020·Frontiers in Pharmacology·Romain LaraShaun McNulty
Sep 18, 2020·Neuroscience·Rashmi Das, Subashchandrabose Chinnathambi
Dec 18, 2020·Molecular Psychiatry·Deidiane Elisa RibeiroHenning Ulrich
Apr 24, 2021·Frontiers in Cellular Neuroscience·Paul R Territo, Hamideh Zarrinmayeh
Apr 30, 2021·Frontiers in Pharmacology·Talita GlaserHenning Ulrich

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Methods Mentioned

BETA
PCR
electron microscopy
scintillation spectroscopy
electrophoresis
coimmunoprecipitation

Software Mentioned

GraphPad Prism
GraphPad

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