biostudies-literatureUnknown13Budgett RFThe 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.Frontiers in pharmacology893422https://www.ebi.ac.uk/biostudies/studies/S-EPMC9130574biostudies-literatureTargeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?PMC9130574Bakker GBradley SJBudgett RFSergeev EBennett KAfalseTargeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?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.2022-01-01T00:00:00Z20222025-04-04T19:31:35.693Z2025-02-19T02:57:51.179ZS-EPMC91305743564579110.3389/fphar.2022.893422