scholarly journals Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease

Brain ◽  
2015 ◽  
Vol 139 (2) ◽  
pp. 526-546 ◽  
Author(s):  
Laura T. Haas ◽  
Santiago V. Salazar ◽  
Mikhail A. Kostylev ◽  
Ji Won Um ◽  
Adam C. Kaufman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prion Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Cellular Prion Protein ◽  
Intracellular Signalling ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate

Noncanonical Metabotropic Glutamate Receptor 5 Signaling in Alzheimer's Disease

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Khaled S. Abd-Elrahman ◽  
Stephen S.G. Ferguson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptor ◽  
Therapeutic Target ◽  
Metabotropic Glutamate Receptor ◽  
Cellular Prion Protein ◽  
Publication Date ◽  
Pathophysiological Mechanism ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate

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. β-Amyloid 42 (Aβ42) 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, sex-specific 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. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease

2014 ◽  
Vol 7 (1) ◽  
pp. 40 ◽  
Author(s):  
Alison Hamilton ◽  
Jessica L Esseltine ◽  
Rebecca A DeVries ◽  
Sean P Cregan ◽  
Stephen S G Ferguson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate ◽  
Model Of Alzheimer’S Disease

IC-04-03: PET IMAGING OF METABOTROPIC GLUTAMATE RECEPTOR 5 BINDING IN ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_1) ◽  
pp. P8-P9
Author(s):  
Adam P. Mecca ◽  
Julia W. McDonald ◽  
Hannah R. Michalak ◽  
Tyler Godek ◽  
Joanna Harris ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptor ◽  
Pet Imaging ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate

Increased prion protein processing and expression of metabotropic glutamate receptor 1 in a mouse model of Alzheimer's disease

2013 ◽  
Vol 127 (3) ◽  
pp. 415-425 ◽  
Author(s):  
Valeriy G. Ostapchenko ◽  
Flavio H. Beraldo ◽  
Andre L. S. Guimarães ◽  
Sanju Mishra ◽  
Monica Guzman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Prion Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Protein Processing ◽  
Metabotropic Glutamate ◽  
Model Of Alzheimer’S Disease ◽  
Metabotropic Glutamate Receptor 1

P1-469: PET IMAGING OF METABOTROPIC GLUTAMATE RECEPTOR 5 BINDING IN ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_9) ◽  
pp. P501-P503 ◽  
Author(s):  
Adam P. Mecca ◽  
Julia W. McDonald ◽  
Hannah R. Michalak ◽  
Tyler Godek ◽  
Joanna Harris ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glutamate Receptor ◽  
Pet Imaging ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate

scholarly journals Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein

Neuron ◽  
2013 ◽  
Vol 79 (5) ◽  
pp. 887-902 ◽  
Author(s):  
Ji Won Um ◽  
Adam C. Kaufman ◽  
Mikhail Kostylev ◽  
Jacqueline K. Heiss ◽  
Massimiliano Stagi ◽  
...  
Keyword(s):  
Prion Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Cellular Prion Protein ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate ◽  
Aβ Oligomer

scholarly journals Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein

Neuron ◽  
2013 ◽  
Vol 80 (2) ◽  
pp. 531 ◽  
Author(s):  
Ji Won Um ◽  
Adam C. Kaufman ◽  
Mikhail Kostylev ◽  
Jacqueline K. Heiss ◽  
Massimiliano Stagi ◽  
...  
Keyword(s):  
Prion Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Cellular Prion Protein ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate ◽  
Aβ Oligomer

scholarly journals Oligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease

2016 ◽  
Vol 291 (33) ◽  
pp. 17112-17121 ◽  
Author(s):  
Laura T. Haas ◽  
Stephen M. Strittmatter
Keyword(s):  
Alzheimer Disease ◽  
Prion Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Brain Slices ◽  
Amyloid Β ◽  
Cellular Prion Protein ◽  
Wild Type ◽  
Metabotropic Glutamate Receptor 5 ◽  
Metabotropic Glutamate

The dysfunction and loss of synapses in Alzheimer disease are central to dementia symptoms. We have recently demonstrated that pathological Amyloid β oligomer (Aβo) regulates the association between intracellular protein mediators and the synaptic receptor complex composed of cellular prion protein (PrPC) and metabotropic glutamate receptor 5 (mGluR5). Here we sought to determine whether Aβo alters the physiological signaling of the PrPC-mGluR5 complex upon glutamate activation. We provide evidence that acute exposure to Aβo as well as chronic expression of familial Alzheimer disease mutant transgenes in model mice prevents protein-protein interaction changes of the complex induced by the glutamate analog 3,5-dihydroxyphenylglycine. We further show that 3,5-dihydroxyphenylglycine triggers the phosphorylation and activation of protein-tyrosine kinase 2-β (PTK2B, also referred to as Pyk2) and of calcium/calmodulin-dependent protein kinase II in wild-type brain slices but not in Alzheimer disease transgenic brain slices or wild-type slices incubated with Aβo. This study further distinguishes two separate Aβo-dependent signaling cascades, one dependent on extracellular Ca2+ and Fyn kinase activation and the other dependent on the release of Ca2+ from intracellular stores. Thus, Aβo triggers multiple distinct PrPC-mGluR5-dependent events implicated in neurodegeneration and dementia. We propose that targeting the PrPC-mGluR5 complex will reverse aberrant Aβo-triggered states of the complex to allow physiological fluctuations of glutamate signaling.

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