DJ-1–Mediated Protective Effect of Protocatechuic Aldehyde Against Oxidative Stress in SH-SY5Y Cells

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DJ-1 was identified as a causal gene for a familial form of early onset Parkinson’s disease (PD), park 7. DJ-1 plays roles in transcriptional regulation and the anti-oxidative stress reaction. In this study, we found that protocatechuic aldehyde (PAL), a traditional Chinese medicine compound, bound to DJ-1 in vitro and that PAL protected SH-SY5Y cells but not DJ-1–knockdown SH-SY5Y cells from oxidative stress–induced cell death, indicating that the protective effect of PAL is mediated by DJ-1. Furthermore, PAL inhibited production of reactive oxygen species and the inhibition was abated in DJ-1–knockdown cells. PAL increased and decreased phosphorylation of AKT and PTEN, respectively, in SH-SY5Y cells, suggesting that the AKT pathway is one of the specific signaling pathways in PAL-induced neuroprotection. Moreover, PAL prevented superfluous oxidation of cysteine 106 of DJ-1, an essential amino acid for DJ-1’s function. The present study demonstrates that PAL has potential neuroprotective effects through DJ-1.