Curcumin reduces α-synuclein induced cytotoxicity in Parkinson's disease cell model

Background: Overexpression and abnormal accumulation of aggregated alpha-synuclein (alpha S) have been linked to Parkinson's disease (PD) and other synucleinopathies. alpha S can misfold and adopt a variety of morphologies but recent studies implicate oligomeric forms alpha S the most cytotoxic species. Both genetic mutations and chronic exposure to neurotoxins increase alpha S aggregation and intracellular reactive oxygen species (ROS), leading to mitochondrial dysfunction and oxidative damage in PD cell models. Results: Here we show that curcumin can alleviate alpha S-induced toxicity, reduce ROS levels and protect cells against apoptosis. We also show that both intracellular overexpression of alpha S and extracellular addition of oligomeric alpha S increase ROS which induces apoptosis, suggesting that aggregated alpha S may induce similar toxic effects whether it is generated intra-or extracellulary. Conclusions: Since curcumin is a natural food pigment that can cross the blood brain barrier and has widespread medicinal uses, it has potential therapeutic value for treating PD and other neurodegenerative disorders.