Melatonin protects dopaminergic neurons in paraquat-induced Parkinson in rats through PI3K/AKT/Nrf2 pathway

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by dopaminergic neuron degeneration and α-synuclein aggregation in the substantia nigra. Melatonin, a widely used neuroregulatory hormone, has shown potential in treating PD, while its precise mechanism of action remains unclear. In this study, we investigated the neuroprotective effects of melatonin (MT) in a paraquat-induced rat model of Parkinson's disease, focusing on oxidative stress and mitochondrial dysfunction. Our findings revealed that paraquat (PQ) induced damage to dopaminergic neurons in the substantia nigra, accompanied by oxidative stress and mitochondrial dysfunction. Treatment with MT alleviated PQ-induced oxidative stress, preserved mitochondrial function, and protected dopaminergic neurons. Additionally, the PI3K/AKT pathway inhibitor LY294002 suppressed the expression of Nrf2 and disrupted the neuroprotective effects of MT. We propose that MT activates Nrf2 via the PI3K/AKT pathway to protect mitochondria and reduce oxidative stress. Our results suggest that the PI3K/AKT/Nrf2 pathway plays a crucial role in the neuroprotective effects of melatonin in Parkinson's disease.