title: 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.
authors.affiliation: Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: León-Otegui
authors.forename: Rosa
authors.initials: R
authors.lastname: Gómez-Villafuertes
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Díaz-Hernández
authors.forename: Miguel
authors.initials: M
authors.lastname: Díaz-Hernández
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Miras-Portugal
authors.forename: Javier
authors.initials: J
authors.lastname: Gualix
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000345:Affinity Labels / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D058914:Purinergic Antagonists / Q000378:metabolism; D034622:RNA Interference; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D058473:Receptors, Purinergic P2Y2 / Q000235:genetics / Q000378:metabolism*; D013498:Suramin / Q000378:metabolism
chemical_list: D000345:Affinity Labels; D016564:Amyloid beta-Protein Precursor; D000970:Antineoplastic Agents; D058914:Purinergic Antagonists; D058486:Receptors, Purinergic P2X7; D058473:Receptors, Purinergic P2Y2; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D053829:Amyloid Precursor Protein Secretases