Targeting the type 5 metabotropic glutamate receptor: a potential therapeutic strategy for neurodegenerative diseases?

Budgett, R. F., Bakker, G., Sergeev, E. , Bennett, K. A. and Bradley, S. J. (2022) Targeting the type 5 metabotropic glutamate receptor: a potential therapeutic strategy for neurodegenerative diseases? Frontiers in Pharmacology, 13, 893422. (doi: 10.3389/fphar.2022.893422) (PMID:35645791) (PMCID:PMC9130574)

Abstract

The type 5 metabotropic glutamate receptor, mGlu5, has been proposed as a potential therapeutic target for the treatment of several neurodegenerative diseases. In preclinical neurodegenerative disease models, novel allosteric modulators have been shown to improve cognitive performance and reduce disease-related pathology. A common pathological hallmark of neurodegenerative diseases is a chronic neuroinflammatory response, involving glial cells such as astrocytes and microglia. Since mGlu5 is expressed in astrocytes, targeting this receptor could provide a potential mechanism by which neuroinflammatory processes in neurodegenerative disease may be modulated. This review will discuss current evidence that highlights the potential of mGlu5 allosteric modulators to treat neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Furthermore, this review will explore the role of mGlu5 in neuroinflammatory responses, and the potential for this G protein-coupled receptor to modulate neuroinflammation.

• Item Type: Articles
• Additional Information: This research was funded by Medical Research Scotland.
• Keywords: Pharmacology, GPCR, Alzheimer’s disease, neurodegenerative disease, neuroinflammation, G protein coupled receptors, drug discovery.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sergeev, Miss Eugenia and Bradley, Dr Sophie and Budgett, Rebecca
• Authors: Budgett, R. F., Bakker, G., Sergeev, E., Bennett, K. A., and Bradley, S. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Frontiers in Pharmacology
• Publisher: Frontiers Media
• ISSN: 1663-9812
• ISSN (Online): 1663-9812
• Copyright Holders: Copyright © 2022 Budgett, Bakker, Sergeev, Bennett and Bradley
• First Published: First published in Frontiers in Pharmacology 13: 893422
• Publisher Policy: Reproduced under a Creative Commons License