M1 muscarinic receptor activation protects neurons from β-amyloid toxicity.: A role for Wnt signaling pathway

被引：68

作者：

Farías, GG

Godoy, JA

Hernández, F

Avila, J

Fisher, A

Inestrosa, NC

机构：

[1] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Ctr FONDAP Regulat Celular & Pathol, MIFAB, Santiago, Chile

[2] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, Madrid 28049, Spain

[3] Israel Inst Biol Res, Dept Med & Organ Chem, IL-74100 Ness Ziona, Israel

来源：

NEUROBIOLOGY OF DISEASE | 2004年 / 17卷 / 02期

关键词：

M1; mAChR; A beta neurotoxicity; GSK-3 beta transgenic mice; Wnt signaling; Alzheimer's disease;

D O I：

10.1016/j.nbd.2004.07.016

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Amyloid-beta-peptide (Abeta) deposits are one of the hallmark features of Alzheimer's disease. Signal transduction alterations are implicate in the neuronal responses to Abeta, which include neurotransmitter systems and pathways involved in the maintenance of the nervous system. In this context, we have recently found that Abeta-neurotoxicity triggers a loss of Wnt signaling. We report here that M1-acetylcholine-muscarinicreceptor (mAChR) activation protects neurons from Abeta-toxicity. Concomitant with this effect, a modulation of the Wnt signaling was observed. M1 mAChR activation inhibits glycogen-synthase-kinase-3beta (GSK-3beta) activity, stabilizes cytoplasmic and nuclear beta-catenin, and induces the expression of the Wnt target genes engrailed and cyclfn-D1, reverting the switch off of the Wnt pathway caused by Abeta-toxicity. Neurons from mice that overexpress GSK-3beta allow us to establish that M1 mAChR stimulation leads to GSK-3beta inactivation. We conclude that the cross-talk between the muscarinic signaling and Wnt components underlie the neuroprotective effect of the M1 mAChR activation. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：337 / 348

页数：12

共 64 条

[31] Acetylcholinesterase-amyloid-β-peptide interaction and Wnt signaling involvement in Aβ neurotoxicity [J].

Inestrosa, NC ;

Alvarez, A ;

Godoy, J ;

Reyes, A ;

De Ferrari, GV .

ACTA NEUROLOGICA SCANDINAVICA, 2000, 102 :53-59

[32] Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer's fibrils: Possible role of the peripheral site of the enzyme [J].

Inestrosa, NC ;

Alvarez, A ;

Perez, CA ;

Moreno, RD ;

Vicente, M ;

Linker, C ;

Casanueva, OI ;

Soto, C ;

Garrido, J .

NEURON, 1996, 16 (04) :881-891

[33]

INESTROSA NC, 2004, IN PRESS CURR ALZHEI

[34]

JOYCE JN, 1989, J NEUROSCI, V9, P2776

[35] Acute stress facilitates long-lasting changes in cholinergic gene expression [J].

Kaufer, D ;

Friedman, A ;

Seidman, S ;

Soreq, H .

NATURE, 1998, 393 (6683) :373-377

[36] Phospholipase C isozymes selectively couple to specific neurotransmitter receptors [J].

Kim, D ;

Jun, KS ;

Lee, SB ;

Kang, NG ;

Min, DS ;

Kim, YH ;

Ryu, SH ;

Suh, PG ;

Shin, HS .

NATURE, 1997, 389 (6648) :290-293

[37] M1 muscarinic receptors block caspase activation by phosphoinositide 3-kinase- and MAPK/ERK-independent pathways [J].

Leloup, C ;

Michaelson, DM ;

Fisher, A ;

Hartmann, T ;

Beyreuther, K ;

Stein, R .

CELL DEATH AND DIFFERENTIATION, 2000, 7 (09) :825-833

[38] Muscarinic acetylcholine receptor expression in memory circuits: Implications for treatment of Alzheimer disease [J].

Levey, AI .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :13541-13546

[39]

LEVEY AI, 1995, J NEUROSCI, V15, P4077

[40] Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation [J].

Lin, L ;

Georgievska, B ;

Mattsson, A ;

Isacson, O .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (21) :12108-12113

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