Suppressing Cdk5 Activity by Luteolin Inhibits MPP+-Induced Apoptotic of Neuroblastoma through Erk/Drp1 and Fak/Akt/GSK3β Pathways

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons. The cause of PD is still unclear. Oxidative stress and mitochondrial dysfunction have been linked to the development of PD. Luteolin, a non-toxic flavonoid, has become interested in an alternative medicine, according to its effects on anti-oxidative stress and anti-apoptosis, although the underlying mechanism of luteolin on PD has not been fully elucidated. This study aims to investigate whether luteolin prevents neurotoxicity induction by 1-methyl-4-phenylpyridinium iodide (MPP+), a neurotoxin in neuroblastoma SH-SY5Y cells. The results reveal that luteolin significantly improved cell viability and reduced apoptosis in MPP+-treated cells. Increasing lipid peroxidation and superoxide anion (O-2(-)), including mitochondrial membrane potential (Delta psi m) disruption, is ameliorated by luteolin treatment. In addition, luteolin attenuated MPP+-induced neurite damage via GAP43 and synapsin-1. Furthermore, Cdk5 is found to be overactivated and correlated with elevation of cleaved caspase-3 activity in MPP+-exposed cells, while phosphorylation of Erk1/2, Drp1, Fak, Akt and GSK3 beta are inhibited. In contrast, luteolin attenuated Cdk5 overactivation and supported phosphorylated level of Erk1/2, Drp1, Fak, Akt and GSK3 beta with reducing in cleaved caspase-3 activity. Results indicate that luteolin exerts neuroprotective effects via Cdk5-mediated Erk1/2/Drp1 and Fak/Akt/GSK3 beta pathways, possibly representing a potential preventive agent for neuronal disorder.

Automated summary

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons with the cause still unclear. Luteolin, a non-toxic flavonoid, has shown potential as an alternative medicine for PD due to its antioxidative and anti-apoptotic effects, as demonstrated in this study. The results suggest that luteolin can prevent neurotoxicity induced by MPP+ in neuroblastoma SH-SY5Y cells by improving cell viability and reducing apoptosis, as well as ameliorating mitochondrial dysfunction and neurite damage. Additionally, luteolin exerts its neuroprotective effects through the regulation of Cdk5-mediated Erk1/2/Drp1 and Fak/Akt/GSK3 beta pathways.