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

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

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

doi

10.1016/j.febslet.2011.05.048

subject

Has Abstract

pub_date

2011-07-21 00:00:00

pages

2255-62

issue

14

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(11)00414-5

journal_volume

585

pub_type

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