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.
Highlights
Parkinson’s disease (PD) is a debilitating neurodegenerative disorder which is second to Alzheimer’s disease as the most common age-related disease
Comprises the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the accumulation of intracytoplasmic inclusions, which are known as Lewy bodies in these neurons [2]
GluN3A, −B, and −C, which assemble in the form of heterodimers or heterotrimers. Because of their high permeability to calcium ions and their ability to trigger a cascade of downstream calcium-dependent signal-transduction processes of physiological and pathophysiological changes, NMDA receptors play an important role in the regulation of excitatory synaptic transmission
Summary
Parkinson’s disease (PD) is a debilitating neurodegenerative disorder which is second to Alzheimer’s disease as the most common age-related disease. Dopamimetic drugs, including the dopamine precursor levodopa (l-3,4-dihydroxyphenylalanine, l-DOPA), and dopamine receptor agonists are currently considered as the only standard therapy for treating Parkinsonian symptoms [3] These treatments ameliorate the motor signs of PD for several years in most patients, prolonged therapy frequently leads to the development of motor complications, known as L-DOPA-induced-dyskinesia (LID), such as choreic or larger amplitude choreo-athetotic movements, dystonia, and ballism [4]. Through are multimeric ion channels and are responsible for fast excitatory transmission in the mammalian binding the presynaptically released glutamate, iGluRs transduce signals into the excitation of CNS. Discuss thecontribute distribution these different subtypes of pathophysiology and the treatment targets we of PD, may to of the development of novel glutamate receptors andtotheir properties, as well as evidence of the pharmacological therapeutic approaches. We discuss the distribution of these different subtypes manipulation these receptors in PD.neuroprotective properties, as well as evidence of the of glutamate ofreceptors and their pharmacological manipulation of these receptors in PD
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