α-Lipoic acid attenuates oxidative stress and neurotoxicity via the ERK/Akt-dependent pathway in the mutant hSOD1 related Drosophila model and the NSC34 cell line of amyotrophic lateral sclerosis

Brain Research Bulletin
Tian-Hang WangHong-Lin Feng

Abstract

Amyotrophic lateral sclerosis (ALS) is a degenerative disease with a progressive loss of motor neurons in the central nervous system (CNS). However, there are unsolved problems with the therapies for this disease. α-Lipoic acid (LA) is a natural, universal antioxidant capable of scavenging hydroxyl radicals as well as regenerating a series of antioxidant enzymes that has been widely used in clinical settings. This study aimed to evaluate the antioxidant and neuroprotective effects of LA in ALS cell and Drosophila models with mutant G85R and G93A hSOD1 genes. The biological effects of LA and the protein levels of several antioxidant factors were examined, as were those of phospho-Akt and phospho-ERK. Furthermore, specific inhibitors of the PI3K/Akt and MEK/ERK signaling pathways were used to analyze their effects on LA-induced antioxidant expression in vivo and in vitro. Evidences showed that the mutant hSOD1 resulted in the increased oxidative stress, abnormal antioxidant signaling and pathological behaviors in motor performance and survival compared with non-mutant hSOD1 models, treatment with LA improved motor activity and survival in transgenic flies, prevented NSC34 cells from mutant hSOD1 or H2O2 induced decreased antioxid...Continue Reading

Citations

Feb 8, 2019·Biological Chemistry·Chantal ChudobaAndré Kleinridders
Feb 2, 2019·Neurotoxicity Research·Sachchida Nand RaiSurya Pratap Singh
Apr 26, 2019·Journal of Cachexia, Sarcopenia and Muscle·Savina ApolloniCinzia Volonté
Feb 16, 2021·Frontiers in Cell and Developmental Biology·Olena OdnokozSvetlana N Radyuk
Jan 23, 2021·International Journal of Molecular Sciences·Sophie LayalleLaurent Soustelle
May 1, 2021·International Journal of Molecular Sciences·Francesco LiguoriCinzia Volonté
Jul 3, 2021·International Journal of Molecular Sciences·Elena ObradorJosé M Estrela
Jul 30, 2021·Cellular and Molecular Life Sciences : CMLS·Francesco LiguoriCinzia Volonté

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