Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. The purpose of this study was to clarify effects of brazilian green propolis and the active ingredient against ALS-associated mutant copper-zinc superoxide dismutase (SOD1)-mediated toxicity. Ethanol extract of brazilian green propolis (EBGP) protected N2a cells against mutant SOD1-induced neurotoxicity and reduced aggregated mutant SOD1 by induction of autophagy. Kaempferide and kaempferol, the active ingredients of EBGP, also inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates. Both kaempferide and kaempferol significantly suppressed mutant SOD1-induced superoxide in mitochondria. Western blot analysis showed that kaempferol potentially induced autophagy via the AMP-activated protein kinase (AMPK) - the mammalian target of rapamycin (mTOR) pathway. These results suggest that EBGP containing the active ingredient against mutant SOD1-mediated toxicity is a promising medicine or health food for prevention and treatment of ALS.
Highlights
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motor neurons and by the formation of intracellular protein aggregations that form in motor neurons
To previous studies[17, 18], western blot analysis showed that triton X-100-insoluble SOD1G85R was increased (Fig. 1D)
AKT phosphorylation was not affected by kaempferol (Fig. 6A,D). These results suggest that kaempferol potentially induces autophagy via the AMPK-mammalian target of rapamycin (mTOR) pathway
Summary
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motor neurons and by the formation of intracellular protein aggregations that form in motor neurons. Mutant SOD1 proteins form insoluble aggregations with components of the ubiquitin proteasome system (UPS) and autophagy pathway in motor neurons[2, 3]. The effect of propolis and the active components against ALS-associated mutant SOD1-mediated toxicity is not well known. To examine whether propolis and the active components have neuroprotective effect against mutant SOD1-induced neurotoxicity in a cellular model, we used the ethanol extract of Brazilian green propolis (EBGP). The ethanol extract of propolis is the major form used in health food[14]. We further investigate whether autophagy is involved in the neuroprotection of kaempferol and kaempferide against mutant SOD1-related neurotoxicity via the AMP-activated protein kinase (AMPK) - the mammalian target of rapamycin (mTOR) pathway
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