The role of s-nitrosylation and s-glutathionylation of protein disulphide isomerase in protein misfolding and neurodegeneration

International Journal of Cell Biology
M HalloranJulie D Atkin

Abstract

Neurodegenerative diseases involve the progressive loss of neurons, and a pathological hallmark is the presence of abnormal inclusions containing misfolded proteins. Although the precise molecular mechanisms triggering neurodegeneration remain unclear, endoplasmic reticulum (ER) stress, elevated oxidative and nitrosative stress, and protein misfolding are important features in pathogenesis. Protein disulphide isomerase (PDI) is the prototype of a family of molecular chaperones and foldases upregulated during ER stress that are increasingly implicated in neurodegenerative diseases. PDI catalyzes the rearrangement and formation of disulphide bonds, thus facilitating protein folding, and in neurodegeneration may act to ameliorate the burden of protein misfolding. However, an aberrant posttranslational modification of PDI, S-nitrosylation, inhibits its protective function in these conditions. S-nitrosylation is a redox-mediated modification that regulates protein function by covalent addition of nitric oxide- (NO-) containing groups to cysteine residues. Here, we discuss the evidence for abnormal S-nitrosylation of PDI (SNO-PDI) in neurodegeneration and how this may be linked to another aberrant modification of PDI, S-glutathionyla...Continue Reading

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Citations

Aug 13, 2014·Archives of Physiology and Biochemistry·Doina Popov
Jan 19, 2016·Frontiers in Cell and Developmental Biology·Emma R PerriJulie D Atkin
Jun 26, 2014·British Journal of Pharmacology·A I SantosI M Araújo
Aug 19, 2015·Neurobiology of Disease·Giovanni Manfredi, Hibiki Kawamata
Apr 2, 2015·Archives of Toxicology·Olga Gorelenkova Miller, John J Mieyal
Jun 9, 2015·Frontiers in Cell and Developmental Biology·Sonam Parakh, Julie D Atkin
May 27, 2017·Molecular Neurodegeneration·Neil T SprenkleGordon P Meares
Feb 20, 2018·Oxidative Medicine and Cellular Longevity·Sun Joo ChaKiyoung Kim
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Albert SerranoKen Teter
Mar 30, 2021·Ageing Research Reviews·Rohan GuptaPravir Kumar
Jul 20, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rüdiger Hardeland
Aug 14, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Fuquan WangHaifa Xia
Sep 3, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Faisal MahmoodJinyang Zhang
Jun 15, 2021·Antioxidants & Redox Signaling·Moua Yang, Robert Flaumenhaft

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Methods Mentioned

BETA
acetylation
protein
transgenic
protein folding

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