Melatonin attenuates MPP⁺-induced apoptosis via heat shock protein in a Parkinson's disease model

Heat shock proteins (HSPs) play an essential role as molecular chaperones to prevent abnormal protein aggregation and misfolding. Moreover, they protect dopamine neurons from oxidative stress, inflammation, and apoptosis, all well-known pathomechanisms of Parkinson's disease (PD). Melatonin is a potent antioxidant that has the beneficial ability to prevent neurodegenerative diseases like PD. We aimed to explore the protective properties of melatonin in an in vitro PD model, focusing on its underlying mechanism using HSPs. A 1-methyl-4-phenylpyridimium (MPP+)-induced toxin model was established with retinoic acid (RA)-differentiated SH-SY5Y cells. Cell viability and apoptosis were measured using MTT and DAPI. Intracellular reactive oxygen species (ROS) levels were measured by the cell-permeant fluorescent probe DCFH-DA. The level of malondialdehyde and the activities of superoxide dismutase and glutathione peroxidase were assessed using ELISA kits. Apoptotic markers of Bax, Bcl2, and cleaved caspase-3, as well as HSP70 and heat shock factor-1 (HSF1), were measured by Western blot. The melatonin effect through HSP70 was tested with silencing of HSF1 in the MPP + -treated SH-SY5Y cells. Melatonin can protect against MPP + -induced neuronal toxicity by promoting anti-oxidative and anti-apoptotic properties. SH-SY5Y cells exposed to melatonin with MPP + showed increased expression of HSP70 and HSF1 compared with those exposed to MPP + alone. However, siRNA-mediated downregulation of HSF1 significantly attenuated the protective effects of melatonin in the MPP + -induced in vitro PD model. Our findings revealed the protective roles of melatonin in an in vitro PD model. Melatonin can hinder the toxic effects of MPP + on dopaminergic neuronal cells via upregulation of the HSF1/HSP70 pathway. Further experimental studies would verify the therapeutic relevance of melatonin with HSP70 and HSF1 to prevent and decelerate PD-like neurodegeneration.