Nicotine protects astrocytes expressing alpha-synuclein against aminochrome cytotoxicity: Implications for Parkinson’s disease

Astrocytes containing alpha-synuclein (α-Syn) are a cytopathological finding in post-mortem samples of patients with Parkinson's disease (PD). Aminochrome, a subproduct of dopamine oxidation, can induce formation of neurotoxic α-Syn oligomers, astrocyte reactivity, and astrocyte cell death. Nicotine, on the other hand, has been shown to have a protective effect against aminochrome cytotoxicity in substantia nigra dopaminergic cells. However, whether nicotine can also protect against aminochrome toxicity in α-Syn-expressing astrocytes is not known. To address this question, we used the human glioblastoma U251 cells stably overexpressing mutant A53T/nYFP α-Syn, and the U251 wild-type cells as a negative control. The results showed that treatments with 10 µM nicotine, for 24 or 48 h, protected U251 cells containing mutant α-Syn against aminochrome-induced cytotoxicity. Cell viability was assessed by MTT, and cleaved Caspase-3 by immunofluorescence. The protective effect of nicotine was also associated with an increase in acidic organelles in U251 cells containing mutant α-Syn. Overall, the results of this study reinforce the pharmacological potential of nicotine as a protective agent against brain cell degeneration especially relevant to PD.