Abstract
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.
Highlights
Amyotrophic lateral sclerosis (ALS) is a rapid, progressive neurodegenerative disease that is characterized by muscle weakness, paralysis, and respiratory failure, leading to death within 3–5 years
The ubiquitin proteasome system (UPS) and autophagy pathway involved in mutant copper–zinc superoxide dismutase 1 proteins (SOD1mut) form insoluble aggregations in motor neurons [4,5]
Our previous study showed that an ethanol extract of Brazilian green propolis (EBGP) and kaempferol contributed to the clearance of SOD1mut aggregations via the activation of the autophagic pathway and that EBGP and kaempferol have a neuroprotective effect against SOD1mut-induced neurotoxicity [23]
Summary
Amyotrophic lateral sclerosis (ALS) is a rapid, progressive neurodegenerative disease that is characterized by muscle weakness, paralysis, and respiratory failure, leading to death within 3–5 years. The ubiquitin proteasome system (UPS) and autophagy pathway involved in mutant copper–zinc superoxide dismutase 1 proteins (SOD1mut) form insoluble aggregations in motor neurons [4,5]. It remains unclear how SOD1mut aggregation causes motor neuron death. It has been reported that the activation of autophagy suppresses motor neuronal cell death through the clearance of SOD1mut aggregations in cellular and mouse models of ALS [14,15]. Our previous study showed that an ethanol extract of Brazilian green propolis (EBGP) and kaempferol contributed to the clearance of SOD1mut aggregations via the activation of the autophagic pathway and that EBGP and kaempferol have a neuroprotective effect against SOD1mut-induced neurotoxicity [23]. Because autophagy is well known as a characteristic event in ALS, we chose p-CA among these active components in EBGP and examined the effects of p-CA against SOD1mut-related toxicity from the viewpoint of autophagy
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