Background Parkinson’s disease (PD) is commonly characterised by motor movement deterioration and cognitive impairment. Salsolinol, a dopamine-derived endogenous neurotoxin, may contribute to PD pathogenesis due to its structural and chemical similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the precise molecular mechanisms of the neurotoxin remain unexplored. Hence, this study aimed to evaluate the toxic effects of salsolinol on SH-SY5Y neuronal cells, focusing on mitophagy and its associated pathways.
Methods SH-SY5Y cells were exposed to salsolinol for toxicity assessment using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and inhibitory concentrations (ICs) were determined for the following assays. Induction of autophagy and mitophagy in the salsolinol-treated SH-SY5Y cells was detected with acridine orange and Mtphagy Dye, respectively. Additionally, an enzyme-linked immunosorbent assay (ELISA) was performed to determine the protein levels of the PINK1/PARKIN-mediated mitophagy pathway and the receptor-mediated mitophagy pathway in salsolinol-treated SH-SY5Y cells.
Results Results reveal that SH-SY5Y cells, when treated with salsolinol (0 to 400 μM) for 24 and 48 hours, significantly elicited dose-dependent neurotoxicity. The upregulation of autophagy and mitophagy coincided with increased levels of proteins related to the PINK1/PARKIN-mediated mitophagy pathway and the receptor-mediated mitophagy pathway when treated with IC₅₀ and IC₇₅ as compared to untreated (UT) and IC₂₅.
Conclusion Our findings suggest that salsolinol induces mitophagy via the PINK1/PARKIN-mediated mitophagy and receptor-mediated mitophagy pathways.