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Acknowledgments This work was supported by NIH grant R01DK092407 Abbreviations (in alphabetical order) 4-HNE 4-hydroxynonenal 15d-PGJ 2 15-deoxy- 12,14 -prostaglandin J 2 AP-1 activator protein-1 As 3+ trivalent arsenite -SMA a-smooth muscle actin ARE antioxidant response element ATRA all-trans retinoic acid BDL bile duct ligation BHMT betaine homocysteine methyltransferase -NF -naphthoflavone BSO buthionine sulfoximine CBS cystathionine synthase CMK Ca 2+ -calmodulin kinase II CNC-bZIP cap n collar-basic leucine zipper proteins CREB c-AMP-response element binding protein DEM diethyl maleate ECM extracellular matrix EpRE electrophile response element GCL glutamate-cysteine ligase GCLC GCL-catalytic subunit GCLM GCL-modifier subunit GGT -glutamyltranspeptidase GPx GSH peroxidase GS GSH synthase GSH glutathione GSSG oxidized GSH HCC hepatocellular carcinoma Hcy homocysteine HGF hepatocyte growth factor HSC hepatic stellate cell iNOS inducible nitric oxide synthase LPS lipopolysaccharide MAT methionine adenosyltransferase MRE metal response element MS methionine synthase MT methyltransferase NFE2 nuclear factor erythroid 2 NO nitric oxide Nrf2 nuclear factor-erythroid 2 related factor 2 PKA protein kinase A PKC protein kinase C RNS reactive nitrogen species RXR retinoid X receptor ROS reactive oxygen species SAH S-adenosylhomocysteine SAMe S-adenosylmethionine TAA thioacetamide TBH tert-butyl hydroquinone TGF-1 transforming growth factor-1 TLR4 toll like receptor 4 TNF tumor necrosis factor UDCA ursodeoxycholic acid Footnotes Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication

By improving cellular energy metabolism, reducing oxidative stress, and promoting neuronal survival, PQQ offers a multifaceted approach to counteracting the pathophysiological factors underlying neurodegeneration