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Nitrosative stress, hypernitrosylation, and autoimmune responses to nitrosylated proteins: new pathways in neuroprogressive disorders Including depression and chronic fatigue syndrome.

Morris, Gerwyn, Berk, Michael, Klein, Hans, Walder, Ken, Galecki, Piotr and Maes, Michael 2016, Nitrosative stress, hypernitrosylation, and autoimmune responses to nitrosylated proteins: new pathways in neuroprogressive disorders Including depression and chronic fatigue syndrome., Molecular neurobiology, vol. In press, pp. 1-21, doi: 10.1007/s12035-016-9975-2.

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Title Nitrosative stress, hypernitrosylation, and autoimmune responses to nitrosylated proteins: new pathways in neuroprogressive disorders Including depression and chronic fatigue syndrome.
Author(s) Morris, Gerwyn
Berk, Michael
Klein, Hans
Walder, Ken
Galecki, Piotr
Maes, Michael
Journal name Molecular neurobiology
Volume number In press
Start page 1
End page 21
Total pages 21
Publisher Springer
Place of publication Berlin, Germany
Publication date 2016
ISSN 1559-1182
Keyword(s) Cytokines
Depression
Immune
Leaky gut
Myalgic encephalomyelitis
Nitric oxide
Nitrosative stress
Summary Nitric oxide plays an indispensable role in modulating cellular signaling and redox pathways. This role is mainly effected by the readily reversible nitrosylation of selective protein cysteine thiols. The reversibility and sophistication of this signaling system is enabled and regulated by a number of enzymes which form part of the thioredoxin, glutathione, and pyridoxine antioxidant systems. Increases in nitric oxide levels initially lead to a defensive increase in the number of nitrosylated proteins in an effort to preserve their function. However, in an environment of chronic oxidative and nitrosative stress (O&NS), nitrosylation of crucial cysteine groups within key enzymes of the thioredoxin, glutathione, and pyridoxine systems leads to their inactivation thereby disabling denitrosylation and transnitrosylation and subsequently a state described as "hypernitrosylation." This state leads to the development of pathology in multiple domains such as the inhibition of enzymes of the electron transport chain, decreased mitochondrial function, and altered conformation of proteins and amino acids leading to loss of immune tolerance and development of autoimmunity. Hypernitrosylation also leads to altered function or inactivation of proteins involved in the regulation of apoptosis, autophagy, proteomic degradation, transcription factor activity, immune-inflammatory pathways, energy production, and neural function and survival. Hypernitrosylation, as a consequence of chronically elevated O&NS and activated immune-inflammatory pathways, can explain many characteristic abnormalities observed in neuroprogressive disease including major depression and chronic fatigue syndrome/myalgic encephalomyelitis. In those disorders, increased bacterial translocation may drive hypernitrosylation and autoimmune responses against nitrosylated proteins.
Language eng
DOI 10.1007/s12035-016-9975-2
Field of Research 110319 Psychiatry (incl Psychotherapy)
111714 Mental Health
1109 Neurosciences
1702 Cognitive Science
Socio Economic Objective 920410 Mental Health
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Springer
Free to Read? No
Persistent URL http://hdl.handle.net/10536/DRO/DU:30084480

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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