Shifting towards a model of mGluR5 dysregulation in schizophrenia: Consequences for future schizophrenia treatment

Neuropharmacology
Natalie MatosinKelly A Newell

Abstract

Metabotropic glutamate receptor subtype 5 (mGluR5), encoded by the GRM5 gene, represents a compelling novel drug target for the treatment of schizophrenia. mGluR5 is a postsynaptic G-protein coupled glutamate receptor strongly linked with several critical cellular processes that are reported to be disrupted in schizophrenia. Accordingly, mGluR5 positive allosteric modulators show encouraging therapeutic potential in preclinical schizophrenia models, particularly for the treatment of cognitive dysfunctions against which currently available therapeutics are largely ineffective. More work is required to support the progression of mGluR5-targeting drugs into the clinic for schizophrenia treatment, although some obstacles may be overcome by comprehensively understanding how mGluR5 itself is involved in the neurobiology of the disorder. Several processes that are necessary for the regulation of mGluR5 activity have been identified, but not examined, in the context of schizophrenia. These processes include protein-protein interactions, dimerisation, subcellular trafficking, the impact of genetic variability or mutations on protein function, as well as epigenetic, post-transcriptional and post-translational processes. It is essential t...Continue Reading

References

Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J P PinS F Heinemann
Dec 1, 1995·Archives of General Psychiatry·J W Olney, N B Farber
May 8, 1995·The Journal of Comparative Neurology·C RomanoJ W Olney
Jan 7, 1993·Nature·T V Bliss, G L Collingridge
Nov 8, 1996·The Journal of Biological Chemistry·C RomanoK L O'Malley
Jul 11, 1998·The Journal of Biological Chemistry·M M LaiS H Snyder
Sep 3, 1998·The Journal of Biological Chemistry·A KatoK Inokuchi
Jan 9, 1999·The Journal of Biological Chemistry·J LiK P Huang
Jul 23, 1999·Progress in Neurobiology·F Bordi, A Ugolini
Oct 19, 1999·Biochimica Et Biophysica Acta·R MochizukiK Murakami
Jan 29, 2000·Biological Psychiatry·S M Richardson-BurnsJ H Meador-Woodruff
Aug 8, 2001·The Journal of Biological Chemistry·L GamaG E Breitwieser
Jul 16, 2002·Pharmacology, Biochemistry, and Behavior·Sudar AlagarsamyP Jeffrey Conn
Aug 15, 2002·Biochemical and Biophysical Research Communications·Hironori SaitoYoshihisa Kurachi

❮ Previous
Next ❯

Citations

Jul 5, 2016·Current Treatment Options in Psychiatry·Gary RemingtonMargaret Hahn
Dec 3, 2016·Neuropharmacology·Graham L CollingridgeDarryle D Schoepp
Mar 16, 2019·Frontiers in Molecular Neuroscience·Arnau Ramos-PratsFrancesco Ferraguti
Jun 15, 2019·Proceedings of the National Academy of Sciences of the United States of America·Silvia PittoloPau Gorostiza
Apr 8, 2020·ACS Pharmacology & Translational Science·Karen J GregoryColleen M Niswender

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here