Neuroinflammation and Dyskinesia: A Possible Causative Relationship?

Brain Sci. 2024 May 20;14(5):514. doi: 10.3390/brainsci14050514.

Abstract

Levodopa (L-DOPA) treatment represents the gold standard therapy for Parkinson's disease (PD) patients. L-DOPA therapy shows many side effects, among them, L-DOPA-induced dyskinesias (LIDs) remain the most problematic. Several are the mechanisms underlying these processes: abnormal corticostriatal neurotransmission, pre- and post-synaptic neuronal events, changes in gene expression, and altered plasticity. In recent years, researchers have also suggested non-neuronal mechanisms as a possible cause for LIDs. We reviewed recent clinical and pre-clinical studies on neuroinflammation contribution to LIDs. Microglia and astrocytes seem to play a strategic role in LIDs phenomenon. In particular, their inflammatory response affects neuron-glia communication, synaptic activity and neuroplasticity, contributing to LIDs development. Finally, we describe possible new therapeutic interventions for dyskinesia prevention targeting glia cells.

Keywords: L-DOPA-induced dyskinesias (LIDs); Parkinson’s disease; levodopa (L-DOPA); neuroinflammation; non-neuronal mechanism.

Publication types

  • Review

Grants and funding

This work was supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006)—A multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022) (BP), by the Italian Ministry of Health, Ricerca Corrente (A.d.I.), and by a grant from NYU Grossman School of Medicine and The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders, which was made possible with support from Marlene and Paolo Fresco (A.C.).