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

被引：51
|
作者：
Leon-Otegui, Miriam [1 ]
Gomez-Villafuertes, Rosa [1 ]
Ignacio Diaz-Hernandez, Juan [1 ]
Diaz-Hernandez, Miguel [1 ]
Teresa Miras-Portugal, Maria [1 ]
Gualix, Javier [1 ]
机构：
[1] Univ Complutense Madrid, Fac Vet, Dept Bioquim, E-28040 Madrid, Spain
来源：
FEBS LETTERS | 2011年 / 585卷 / 14期
关键词：
Alzheimer's disease; Amyloid precursor protein processing; alpha-Secretase; P2X7; receptor; P2Y(2) receptor; Neuro-2a; PURINERGIC P2X(7) RECEPTOR; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; BETA PEPTIDE; MICROGLIA; PHARMACOLOGY; INHIBITION; THERAPY; MODEL;
D O I：
10.1016/j.febslet.2011.05.048
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The amyloid precursor protein (APP) is proteolytically processed by beta- and gamma-secretases to release amyloid-beta peptide (Ab), the main component found in senile plaques of Alzheimer's disease (AD) patient brains. Alternatively, APP can be cleaved within the A beta sequence by alpha-secretase, thus precluding the generation of A beta. We have demonstrated that activation of the P2X7 receptor leads to a reduction of alpha-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 alpha-secretase activity. Our study suggests that P2X7R and P2Y(2)R could be novel therapeutic targets in AD. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：2255 / 2262
页数：8
相关论文
共 50 条
  • [21] Loss of P2Y2 Nucleotide Receptors Enhances Early Pathology in the TgCRND8 Mouse Model of Alzheimer's Disease
    Ajit, Deepa
    Woods, Lucas T.
    Camden, Jean M.
    Thebeau, Christina N.
    El-Sayed, Farid G.
    Greeson, Glen W.
    Erb, Laurie
    Petris, Michael J.
    Miller, Douglas C.
    Sun, Grace Y.
    Weisman, Gary A.
    MOLECULAR NEUROBIOLOGY, 2014, 49 (02) : 1031 - 1042
  • [22] Current knowledge on the nucleotide agonists for the P2Y2 receptor
    Xu, Pengfei
    Feng, Xi
    Luan, Hongyu
    Wang, Jubo
    Ge, Raoling
    Li, Zhiyu
    Bian, Jinlei
    BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 26 (02) : 366 - 375
  • [23] Protective effects of P2X7 receptor deletion on aging-related memory alterations
    Lee, Sang-Rim
    Cho, Woo-Hyun
    Lee, Jae-Ran
    Han, Jung-Soo
    GENES & GENOMICS, 2016, 38 (05) : 459 - 465
  • [24] P2X7 receptors exhibit at least three modes of allosteric antagonism
    Oken, Adam C.
    Ditter, Ismayn A.
    Lisi, Nicolas E.
    Krishnamurthy, Ipsita
    Godsey, Michael H.
    Mansoor, Steven E.
    SCIENCE ADVANCES, 2024, 10 (40):
  • [25] P2X7 Receptors: Channels, Pores and More
    Volonte, C.
    Apolloni, S.
    Skaper, S. D.
    Burnstock, G.
    CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2012, 11 (06) : 705 - 721
  • [26] Microglia: Proliferation and activation driven by the P2X7 receptor
    Monif, Mastura
    Burnstock, Geoffrey
    Williams, David A.
    INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2010, 42 (11) : 1753 - 1756
  • [27] The P2X7 Receptor
    Sluyter, Ronald
    PROTEIN REVIEWS, VOL 19, 2017, 1051 : 17 - 53
  • [28] Roles of purinergic P2X7 receptor in glioma and microglia in brain tumors
    McLarnon, James G.
    CANCER LETTERS, 2017, 402 : 93 - 99
  • [29] P2X7 receptors on microglial cells mediate injury to cortical neurons in vitro
    Skaper, Stephen D.
    Facci, Laura
    Culbert, Ainsley A.
    Evans, Nicholas A.
    Chessell, Iain
    Davis, John B.
    Richardson, Jill C.
    GLIA, 2006, 54 (03) : 234 - 242
  • [30] Silencing of the P2X7 receptor enhances amyloid-β phagocytosis by microglia
    Ni, Jiong
    Wang, Peijun
    Zhang, Jingfa
    Chen, Wei
    Gu, Limin
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2013, 434 (02) : 363 - 369
12345