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Opposite effects of P2X7 and P2Y 2 nucleotide receptors on α‐secretase‐dependent APP processing in Neuro‐2a cells
Author(s) -
León-Otegui Miriam,
Gómez-Villafuertes Rosa,
Díaz-Hernández Juan Ignacio,
Díaz-Hernández Miguel,
Miras-Portugal Maria Teresa,
Gualix Javier
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.05.048
Subject(s) - amyloid precursor protein , receptor , amyloid precursor protein secretase , senile plaques , p2y receptor , chemistry , microbiology and biotechnology , alzheimer's disease , peptide , amyloid (mycology) , alpha secretase , neuroscience , biochemistry , biology , medicine , disease , purinergic receptor , inorganic chemistry
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.