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    FEBS Lett. 2011 Jul 21;585(14):2255-62. Epub 2011 Jun 2.

    Opposite effects of P2X7 and P2Y2 nucleotide receptors on α-secretase-dependent APP processing in Neuro-2a cells.

    León-Otegui M, Gómez-Villafuertes R, Díaz-Hernández JI, Díaz-Hernández M, Miras-Portugal MT, Gualix J.

    Source

    Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.

    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.

    PMID:
    21651910
    [PubMed - indexed for MEDLINE]

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