1-P-052
p-クマル酸の変異SOD1毒性に対する神経保護効果
p-Coumaric Acid Has Protective Effects against Mutant Copper–Zinc Superoxide Dismutase 1 via the Activation of Autophagy
〇位田 雅俊、上田 智之、伊藤 泰生、栗田 尚佳、保住 功
Masatoshi Inden, Tomoyuki Ueda, Taosei Ito, Hisaka Kurita, Isao Hozumi
岐阜薬科大・薬
Lab. Med. Therap. Mol. Therap., Gifu Pharm. Univ.
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 (SOD1mut)-induced neurotoxicity. This paper aims to reveal the effects of p-coumaric acid (p-CA), an active ingredient contained in EBGP, against SOD1mut-induced neurotoxicity. We found that p-CA reduced the accumulation of SOD1mut subcellular aggregation and prevented SOD1mut-associated neurotoxicity. Moreover, p-CA attenuated SOD1mut-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 SOD1mut-induced neurotoxicity through the activation of autophagy and provides a potential therapeutic approach for ALS.