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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons. In previous our study, an ethanol extract of Brazilian green propolis (EBGP) prevented mutant copper-zinc superoxide dismutase 1 (SOD1 mut )-induced neurotoxicity. This paper aims to reveal the effects of p-coumaric acid (p-CA), an active ingredient contained in EBGP, against SOD1 mut -induced neurotoxicity. We found that p-CA reduced the accumulation of SOD1 mut subcellular aggregation and prevented SOD1 mut -associated neurotoxicity. Moreover, p-CA attenuated SOD1 mut -induced oxidative stress and endoplasmic reticulum stress, which are significant features in ALS pathology. To examine the mechanism of neuroprotective effects, we focused on autophagy, and we found that p-CA induced autophagy. Additionally, the neuroprotective effects of p-CA were inhibited by chloroquine, an autophagy inhibiter. Therefore, these results obtained in this paper suggest that p-CA prevents SOD1 mut -induced neurotoxicity through the activation of autophagy and provides a potential therapeutic approach for ALS.

p-Coumaric Acid Has Protective Effects against Mutant Copper–Zinc Superoxide Dismutase 1 via the Activation of Autophagy in N2a Cells