Abstract
The amyloid precursor protein (APP) is proteolytically processed by β- and γ-secretases to release amyloid-β peptide (Aβ), the main component found in senile plaques of Alzheimer's disease (AD) patient brains. Alternatively, APP can be cleaved within the Aβ sequence by α-secretase, thus precluding the generation of Aβ. We have demonstrated that activation of the P2X7 receptor leads to a reduction of α-secretase activity in Neuro-2a cells. Moreover, the P2X7 ligand 2'(3')-O-(4-benzoylbenzoyl) ATP (BzATP) can also activate a different P2 receptor in these cells. This receptor, whose pharmacology resembles that of the P2Y(2) receptor, has an opposite effect, leading to increases in α-secretase activity. Our study suggests that P2X7R and P2Y(2)R could be novel therapeutic targets in AD.
Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / metabolism
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Affinity Labels / metabolism
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Alzheimer Disease / metabolism
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Amyloid Precursor Protein Secretases / metabolism*
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Amyloid beta-Protein Precursor / genetics
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Amyloid beta-Protein Precursor / metabolism*
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Animals
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Antineoplastic Agents / metabolism
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Cell Line
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Humans
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Purinergic Antagonists / metabolism
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RNA Interference
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Receptors, Purinergic P2X7 / genetics
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Receptors, Purinergic P2X7 / metabolism*
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Receptors, Purinergic P2Y2 / genetics
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Receptors, Purinergic P2Y2 / metabolism*
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Suramin / metabolism
Substances
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Affinity Labels
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Amyloid beta-Protein Precursor
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Antineoplastic Agents
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Purinergic Antagonists
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Receptors, Purinergic P2X7
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Receptors, Purinergic P2Y2
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3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
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Suramin
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Adenosine Triphosphate
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Amyloid Precursor Protein Secretases