Glutamatergic dysfunction in neurodegenerative diseases focusing on Parkinson's disease: Role of glutamate modulators

Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disorder resulting from the degeneration of dopamenergic neurons in the substantia nigra pars compacta (SNpc). Research has predominantly centered on understanding the dysfunction of dopaminergic neurotransmission in PD. Recently, more studies discussed the potential role of other neurotransmitters in PD neuropathology. One of the most important non-dopaminergic neurotransmitters involved in the pathogenesis of PD is glutamate, which is widely involved in glutamatergic neurotransmission in different brain regions, including SNpc. The development and progression of PD neuropathology and levodopa-induced dyskinesias (LID) are associated with glutamate neurotoxicity. Therefore, this review seeks to explore the possible involvement of glutamatergic signaling in PD development and assess the therapeutic potential of glutamate receptor antagonists in treating the disorder. • Glutamate excitotoxicity in neurodegenerative diseases. • Role of glutamate neurotransmission and antagonists in PD. • Role of glutamate modulators in PD disease. • Role of glutamate excitotoxicity in L-DOPA-induced dyskinesia.