P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein-induced ATP release in neuroblastoma SH-SY5Y cells
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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 to pannexin 1 recruitment to form an active complex responsible for ATP release; and (iii) ASN greatly decreases the activity of extracellular ecto-ATPase responsible for ATP degradation. Thus, it is concluded that purinergic receptors might be putative pharmacological targets in the molecular mechanism of extracellular ASN toxicity. Interference with P2X7 signaling seems to be a promising strategy for the prevention or therapy of PD and other neurodegenerative disorders.
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α-synuclein induces mitochondrial dysfunction and microglial activation caused by P2X7 receptor stimulation.
“Although these symptoms might not be disease-related, studies show that α-synuclein induces mitochondrial dysfunction and microglial activation caused by P2X7 receptor stimulation [143, 144].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [143]
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- Authors
- Wilkaniec, A., Gąssowska, M., Czapski, G. A., Cieślik, M., Sulkowski, G., & Adamczyk, A.
- Affiliations
- Mossakowski Medical Research Institute, Polish Academy of Sciences (PL)
- Corresponding author
- Wilkaniec, Anna
- Venue
- Purinergic Signalling
- Published
- 2017-05-17
- Volume
- 13
- Issue
- 3
- Pages
- 347-361
- ISSN
- 1573-9538 (ISSN-L)
- 1573-9546
- PMC
- PMC5563296
- OpenAlex
- W2614544395
- Cited by
- 61
- References
- 104
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 6 · 2023: 3 · 2022: 10 · 2021: 7 · 2020: 9 · 2019: 4 · 2018: 8 · 2017: 1
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Purinergic Signalling (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Narodowe Centrum Nauki (PL) (2013/09/D/NZ3/0135)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- alpha-synuclein, P2X7 receptor, pannexin 1, ATP release, purinergic signaling, calcium mobilization, ecto-ATPase, neurodegenerative diseases, Parkinson's disease, Lewy bodies, SH-SY5Y cells, synaptoneurosomes
- MeSH terms
- Adenosine Triphosphate, Animals, Calcium, Extracellular Space, Humans, Male, Nerve Tissue Proteins, Rats, Wistar, Microglia, Connexins, Cell Line, Tumor, alpha-Synuclein, Receptors, Purinergic P2X7
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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