Revisiting the idea that amyloid-β peptide acts as an agonist for P2X7

Bibič, Lučka and Stokes, Leanne ORCID: (2020) Revisiting the idea that amyloid-β peptide acts as an agonist for P2X7. Frontiers in Molecular Neuroscience, 13. ISSN 1662-5099

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The P2X7 receptor (P2X7) is a cell surface ligand-gated ion channel, activated by its physiological nucleotide agonist ATP and a synthetic analog (BzATP). However, it has also been suggested that there may be structurally unrelated, non-nucleotide agonists such as the amyloidogenic β peptide. Here we aimed to reassess the effect of amyloid β peptides in various in vitro cell models, namely HEK293 overexpressing human P2X7, the microglial BV-2 cell line, and BV-2 cells lacking P2X7. We measured YO-PRO-1 dye uptake in response to full-length amyloid β peptide (1–42) or the shorter amyloid β peptide (25–35) and there was a concentration-dependent increase in YO-PRO-1 dye uptake in HEK-hP2X7 cells. However, these amyloid β peptide-induced increases in YO-PRO-1 dye uptake were also identical in non-transfected HEK-293 cells. We could observe small transient increases in [Ca2+]i induced by amyloid β peptides in BV-2 cells, however these were identical in BV-2 cells lacking P2X7. Furthermore, our metabolic viability and LDH release experiments suggest no significant change in viability or cell membrane damage in HEK-hP2X7 cells. In the BV-2 cells we found that high concentrations of amyloid β peptides (1–42) and (25–35) could reduce cell viability by up to 35% but this was also seen in BV-2 cells lacking P2X7. We found no evidence of LDH release by amyloid β peptides. In summary, we found no evidence that amyloid β peptides act as agonists of P2X7 in our in vitro models. Our study raises the possibility that amyloid β peptides simply mimic features of P2X7 activation.

Item Type: Article
Uncontrolled Keywords: alzheimer disease,amyloid beta peptide,microglia,p2x7 receptor,reproducibility,molecular biology,cellular and molecular neuroscience ,/dk/atira/pure/subjectarea/asjc/1300/1312
Faculty \ School: Faculty of Science > School of Pharmacy
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Depositing User: LivePure Connector
Date Deposited: 16 Oct 2020 23:58
Last Modified: 22 Oct 2022 07:18
DOI: 10.3389/fnmol.2020.00166


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