Comparative neurochemical and neuroprotective effects of lauric acid, ribose-cysteine, and levodopa in an α-synuclein Drosophila model of Parkinson's disease.

Parkinson's disease (PD) entails dopaminergic neuronal loss in a gradual manner, which is typically linked to oxidative stress, neuroinflammation, and the neurotransmitter homeostasis disruption. This research compares the neurochemical and neuroprotective impacts of lauric acid (LA), ribose-cysteine (RC), and levodopa (LD) in a transgenic Drosophila melanogaster model where human α-synuclein (α-syn) was expressed in dopaminergic neurons. The transgenic flies received treatment with LA, RC, or LD (250 mg/kg diet) for three weeks and were then evaluated by behavioral assays in conjunction with biochemical and molecular analyses of redox status, inflammatory and apoptotic signaling, neurotransmitter levels, and dopaminergic gene expression. Expression of α-syn caused significant deficiencies of locomotor behavior, oxidative damage, activation of neuroinflammation, changes of dopamine, GABA, and glutamate levels, and reduction of dopa decarboxylase expression. All interventions led to substantial increments in behavioral outcomes and oxidative stress status when compared to untreated PD flies. Out of the three treatments, the RC-induced effects on total antioxidant capacity and cell viability were most notable, along with reduction of lipid peroxidation, TNF-α, and caspase-3 activity. LD was the best at restoring locomotor performance and dopamine levels, whereas LA and RC were more potent at apoptotic signaling reduction and dopaminergic gene expression enhancement. Overall, RC effected broader neurochemical modulation than LA across most parameters. The results from this study suggest that LA, RC, and LD have different yet complementary neuroprotective effects in α-syn-induced neurotoxicity and that RC is particularly effective in modulating oxidative and inflammatory pathways that are involved in PD pathophysiology.