Caffeic Acid and Resveratrol Ameliorate Cellular Damage in Cell and Drosophila Models of Spinocerebellar Ataxia Type 3 through Upregulation of Nrf2 Pathway.

Caffeic Acid and Resveratrol Ameliorate Cellular Damage in Cell and Drosophila Models of Spinocerebellar Ataxia Type 3 through Upregulation of Nrf2 Pathway.
Free Radic Biol Med. 2017 Dec 13;:
Authors: Wu YL, Chang JC, Lin WY, Li CC, Hsieh M, Chen HW, Wang TS, Wu WT, Liu CS, Liu KL
Abstract
Polyglutamine (polyQ)-expanded mutant ataxin-3 protein, which is prone to misfolding and aggregation, leads to cerebellar neurotoxicity in spinocerebellar ataxia type 3 (SCA3), an inherited PolyQ neurodegenerative disease. Although the exact mechanism is unknown, the pathogenic effects of mutant ataxin-3 are associated with dysregulation of transcription, protein degradation, mitochondrial function, apoptosis, and antioxidant potency. In the present study we explored the protective role and possible mechanism of caffeic acid (CA) and resveratrol (Res) in cells and Drosophila expressing mutant ataxin-3. Treatment with CA and Res increased the levels of antioxidant and autophagy protein expression with consequently corrected levels of reactive oxygen species, mitochondrial membrane potential, mutant ataxin-3, and the aggregation of mutant ataxin-3 in SK-N-SH-MJD78 cells. Moreover, in SK-N-SH-MJD78 cells, CA and Res enhanced the transcriptional activity of nuclear factor erythroid-derived-2-like 2 (Nrf2), a master transcription factor that upregulates the expression of antioxidant defense genes and the autophagy gene p62. CA and Res improved survival ...

Source: Free Radical Biology and Medicine - December 13, 2017 Category: Biology Authors: Wu YL, Chang JC, Lin WY, Li CC, Hsieh M, Chen HW, Wang TS, Wu WT, Liu CS, Liu KL Tags: Free Radic Biol Med Source Type: research