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 Lettjournal_title
FEBS lettersauthors
León-Otegui M,Gómez-Villafuertes R,Díaz-Hernández JI,Díaz-Hernández M,Miras-Portugal MT,Gualix Jdoi
10.1016/j.febslet.2011.05.048subject
Has Abstractpub_date
2011-07-21 00:00:00pages
2255-62issue
14eissn
0014-5793issn
1873-3468pii
S0014-5793(11)00414-5journal_volume
585pub_type
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