Roles of Glutamate Receptors in Parkinson's Disease

Int J Mol Sci. 2019 Sep 6;20(18):4391. doi: 10.3390/ijms20184391.

Abstract

Parkinson's disease is a progressive neurodegenerative disorder resulting from the degeneration of pigmented dopaminergic neurons in the substantia nigra pars compacta. It induces a series of functional modifications in the circuitry of the basal ganglia nuclei and leads to severe motor disturbances. The amino acid glutamate, as an excitatory neurotransmitter, plays a key role in the disruption of normal basal ganglia function regulated through the interaction with its receptor proteins. It has been proven that glutamate receptors participate in the modulation of neuronal excitability, transmitter release, and long-term synaptic plasticity, in addition to being related to the altered neurotransmission in Parkinson's disease. Therefore, they are considered new targets for improving the therapeutic strategies used to treat Parkinson's disease. In this review, we discuss the biological characteristics of these receptors and demonstrate the receptor-mediated neuroprotection in Parkinson's disease. Pharmacological manipulation of these receptors during anti-Parkinsonian processes in both experimental studies and clinical trials are also summarized.

Keywords: NMDA receptor; Parkinson’s disease; glutamate receptors; mGluR4; mGluR5.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Drug Discovery
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Gene Expression Regulation / drug effects
  • Glutamic Acid / metabolism
  • Humans
  • Molecular Targeted Therapy
  • Neurotransmitter Agents / metabolism
  • Parkinson Disease / drug therapy
  • Parkinson Disease / etiology*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / metabolism*
  • Signal Transduction / drug effects
  • Substantia Nigra / metabolism
  • Synaptic Transmission
  • Treatment Outcome

Substances

  • Excitatory Amino Acid Antagonists
  • Neurotransmitter Agents
  • Receptors, Glutamate
  • Glutamic Acid