Targeting mGluR group III for the treatment of neurodegenerative diseases: Biomedicine and Pharmacotherapy

N. Rabeh, B. Hajjar, J.O. Maraka, A.F. Sammanasunathan, M. Khan, S.M.I. Alkhaaldi, S. Mansour, R.T. Almheiri, H. Hamdan, K.S. Abd-Elrahman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Glutamate, an excitatory neurotransmitter, is essential for neuronal function, and it acts on ionotropic or metabotropic glutamate receptors (mGluRs). A disturbance in glutamatergic signaling is a hallmark of many neurodegenerative diseases. Developing disease-modifying treatments for neurodegenerative diseases targeting glutamate receptors is a promising avenue. The understudied group III mGluR 4, 6–8 are commonly found in the presynaptic membrane, and their activation inhibits glutamate release. Thus, targeted mGluRs therapies could aid in treating neurodegenerative diseases. This review describes group III mGluRs and their pharmacological ligands in the context of amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's diseases. Attempts to evaluate the efficacy of these drugs in clinical trials are also discussed. Despite a growing list of group III mGluR-specific pharmacological ligands, research on the use of these drugs in neurodegenerative diseases is limited, except for Parkinson's disease. Future efforts should focus on delineating the contribution of group III mGluR to neurodegeneration and developing novel ligands with superior efficacy and a favorable side effect profile for the treatment of neurodegenerative diseases. © 2023 The Authors
Original languageBritish English
JournalBiomed. Pharmacother.
Volume168
DOIs
StatePublished - 2023

Keywords

  • Cognitive function
  • Glutamate
  • GPCR
  • MGluR
  • Motor function
  • Neurodegeneration
  • Glutamic Acid
  • Humans
  • Neurodegenerative Diseases
  • Neurons
  • Neurotransmitter Agents
  • Receptors, Metabotropic Glutamate
  • Signal Transduction
  • metabotropic receptor 3
  • metabotropic receptor agonist
  • metabotropic receptor antagonist
  • agents interacting with transmitter, hormone or drug receptors
  • glutamic acid
  • metabotropic receptor
  • allosterism
  • Alzheimer disease
  • amyotrophic lateral sclerosis
  • clinical trial (topic)
  • degenerative disease
  • drug efficacy
  • EC50
  • human
  • Huntington chorea
  • IC50
  • nonhuman
  • Parkinson disease
  • Review
  • signal transduction
  • nerve cell
  • physiology

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