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Noncanonical Metabotropic Glutamate Receptor 5 Signaling in Alzheimer's Disease

被引：50
作者：
Abd-Elrahman, Khaled S. [1 ,2 ,3 ]
Ferguson, Stephen S. G. [1 ,2 ]
机构：
[1] Univ Ottawa, Brain & Mind Res Inst, Ottawa, ON K1H 8M5, Canada
[2] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada
[3] Alexandria Univ, Fac Pharm, Dept Pharmacol & Toxicol, Alexandria 21521, Egypt
来源：
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY | 2022年 / 62卷
关键词：
mGluR5; synaptic plasticity; Alzheimer's disease; amyloid beta; tau; sex differences; N-TERMINAL KINASE; CELLULAR PRION PROTEIN; AMYLOID-BETA OLIGOMERS; FACTOR-KAPPA-B; GLYCOGEN-SYNTHASE KINASE-3-BETA; CULTURED STRIATAL NEURONS; SYNAPTIC PLASTICITY; ALLOSTERIC MODULATION; MOUSE MODEL; FRAGILE-X;
D O I：
10.1146/annurev-pharmtox-021821-091747
中图分类号：
R9 [药学];
学科分类号：
100702 [药剂学];
摘要：
Metabotropic glutamate receptor 5 (mGluR5) is ubiquitously expressed in brain regions responsible for memory and learning. It plays a key role in modulating rapid changes in synaptic transmission and plasticity. mGluR5 supports long-term changes in synaptic strength by regulating the transcription and translation of essential synaptic proteins. beta-Amyloid 42 (A beta 42) oligomers interact with a mGluR5/cellular prion protein (PrPC) complex to disrupt physiological mGluR5 signal transduction. Aberrant mGluR5 signaling and associated synaptic failure are considered an emerging pathophysiological mechanism of Alzheimer's disease (AD). Therefore, mGluR5 represents an attractive therapeutic target for AD, and recent studies continue to validate the efficacy of various mGluR5 allosteric modulators in improving memory deficits and mitigating disease pathology. However, sexspecific differences in the pharmacology of mGluR5 and activation of noncanonical signaling downstream of the receptor suggest that its utility as a therapeutic target in female AD patients needs to be reconsidered.
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收藏
页码：235 / 254
页数：20
相关论文
共 148 条
[1]
Aβ oligomers induce pathophysiological mGluR5 signaling in Alzheimer's disease model mice in a sex-selective manner [J].
Abd-Elrahman, Khaled S. ;
Albaker, Awatif ;
de Souza, Jessica M. ;
Ribeiro, Fabiola M. ;
Schlossmacher, Michael G. ;
Tiberi, Mario ;
Hamilton, Alison ;
Ferguson, Stephen S. G. .
SCIENCE SIGNALING, 2020, 13 (662)
[2]
mGluR5 Contribution to Neuropathology in Alzheimer Mice Is Disease Stage-Dependent [J].
Abd-Elrahman, Khaled S. ;
Hamilton, Alison ;
Albaker, Awatif ;
Ferguson, Stephen S. G. .
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, 2020, 3 (02) :334-344
[3]
Modulation of mTOR and CREB pathways following mGluR5 blockade contribute to improved Huntington's pathology in zQ175 mice [J].
Abd-Elrahman, Khaled S. ;
Ferguson, Stephen S. G. .
MOLECULAR BRAIN, 2019, 12 (1)
[4]
Autophagy is increased following either pharmacological or genetic silencing of mGluR5 signaling in Alzheimer's disease mouse models [J].
Abd-Elrahman, Khaled S. ;
Hamilton, Alison ;
Vasefi, Maryam ;
Ferguson, Stephen S. G. .
MOLECULAR BRAIN, 2018, 11
[5]
D mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington's disease [J].
Abd-Elrahman, Khaled S. ;
Hamilton, Alison ;
Hutchinson, Shaunessy R. ;
Liu, Fang ;
Russell, Ryan C. ;
Ferguson, Stephen S. G. .
SCIENCE SIGNALING, 2017, 10 (510)
[6]
NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin [J].
Alagarsamy, S ;
Saugstad, J ;
Warren, L ;
Mansuy, IM ;
Gereau, RW ;
Conn, PJ .
NEUROPHARMACOLOGY, 2005, 49 :135-145
[7]
Tau pathology involves protein phosphatase 2A in Parkinsonism-dementia of Guam [J].
Arif, Mohammad ;
Kazim, Syed Faraz ;
Grundke-Iqbal, Inge ;
Garruto, Ralph M. ;
Iqbal, Khalid .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (03) :1144-1149
[8]
Detailed In Vitro Pharmacological Characterization of Clinically Tested Negative Allosteric Modulators of the Metabotropic Glutamate Receptor 5 [J].
Arsova, Angela ;
Moller, Thor C. ;
Vedel, Line ;
Hansen, Jakob Lerche ;
Foster, Simon R. ;
Gregory, Karen J. ;
Brauner-Osborne, Hans .
MOLECULAR PHARMACOLOGY, 2020, 98 (01) :49-60
[9]
Awad H, 2000, J NEUROSCI, V20, P7871
[10]
Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression [J].
Banko, JL ;
Hou, LF ;
Poulin, F ;
Sonenberg, N ;
Klann, E .
JOURNAL OF NEUROSCIENCE, 2006, 26 (08) :2167-2173
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