Two Sides of The Same Coin in The Levodopa Treatment of Parkinson's Disease

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder. PD is a characterized by selective loss of dopaminergic neurons in the pars compacta of the substantia nigra. Levodopa (L-dopa) and dopamine agonists have been most commonly used for symptomatic treatment. Since its initial introduction in 1967, L-dopa has been shown to be the most effective pharmacological agent. Thus, L-dopa has been regarded as the gold standard treatment of PD.

First, there are discrepancies between clinical and experimental data with respect to the neuroprotective effects of these drugs on dopaminergic neurons. My study demonstrated that both L-dopa and PPX had comparable neuroprotective properties for dopaminergic neurons in MPTP- treated PD animal models, through modulation of cell survival and apoptotic pathways. Second, the CSF total homocysteine (Hcy) concentration was higher in patients with PD before L-dopa treatment than in controls, and Hcy concentration increased after administration of L-dopa. Elevation of the Hcy concentration in plasma has been implicated in neurodegeneration in patients with stroke, dementia, Alzheimer disease, and Parkinson disease. However, the underlying cellular mechanisms by which elevated Hcy can promote neuronal death is not clear. The present study investigated the effects of Hcy on neural progenitor cells (NPCs) both in vitro and in vivo. I found that Hcy export from astrocytes was induced by the COMT substrates L-dopa. So, I have examined the role of NMDA receptor-mediated activation of the extracellular signal-regulated kinase-mitogen-activated protein (ERK-MAP) kinase pathway in Hcy - dependent neurotoxicity on NPCs in isolated from the postnatal subventricular zone (SVZ) and in PD animal model.