Correlations between neuroinflammation, N-methyl-D-aspartic acid receptors, and levodopa-induced dyskinesia

Mutual activation of microglia and astrocytes and the release of inflammatory factors, such as tumor necrosis factor alpha (TNF-a) and interleukin 1 beta (IL-1b). The release of inflammatory factors promotes the expression of the GluN1 and GluN2 subunits of the N-methyl-D-aspartic acid receptors (NMDAR) in postsynaptic neurons, allowing the binding of excitatory neuronal glutamate (Glu) and NMDAR released from presynaptic neurons and the inward flow of calcium ions (Ca²⁺) to act on neuronal synaptic plasticity by regulating the long-term potentiation (LTP) and MAPK/ERK phosphorylation pathways (also known as the Ras-Raf-MEK-ERK pathway, a chain of proteins in the cell that communicates a signal from a cell surface receptor to the DNA in the nucleus of the cell) through calmodulin-dependent kinase II (CaMKII). The release of inflammatory factors, on the other hand, directly promotes the development of neuroinflammation in the brain, secondary to the death of dopaminergic neurons, which leads to the development of Parkinson disease and the development of levodopa-induced dyskinesia (LID) in patients with Parkinson disease after years of L-DOPA administration by exacerbating the inflammatory response in the brain tissue and, thus, creating a vicious circle. (Source: Zhang J, Luo L, Long E, Chen L. Neurotoxicity induced by taxane-derived drugs: analysis of the FAERS database 2017-2021. Expert Opin Drug Saf 2023;22[8]:715-24. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)