Morris, Gerwyn, Berk, Michael, Klein, Hans et al. · Molecular neurobiology · 2017 · DOI
This study proposes that ME/CFS may be caused by a harmful process called 'hypernitrosylation,' where a molecule called nitric oxide damages proteins in cells, particularly those responsible for producing energy and fighting infections. When this damage becomes chronic, it can disable the body's natural repair systems and trigger the immune system to attack the body's own proteins. The researchers suggest this process could explain many ME/CFS symptoms, including fatigue, cognitive problems, and how bacterial toxins may trigger or worsen the disease.
Understanding potential mechanisms underlying ME/CFS is critical for developing targeted treatments. If hypernitrosylation and nitrosative stress are confirmed as central pathways in ME/CFS, this could lead to therapies targeting nitric oxide metabolism, antioxidant system restoration, or immune tolerance—offering hope for patients who currently lack effective disease-modifying treatments. This framework also suggests potential biomarkers (nitrosylated proteins, nitrosative stress markers) that could improve diagnosis and treatment monitoring.
This is a theoretical review and does not present direct experimental evidence that hypernitrosylation causes ME/CFS. It does not establish causation—only proposes a plausible mechanistic pathway—and does not confirm that nitrosylated protein autoimmunity is the primary driver of ME/CFS pathology. The proposal remains largely inferential and requires direct empirical validation in ME/CFS patient populations.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Morris, Gerwyn, Berk, Michael, Klein, Hans, Walder, Ken, Galecki, Piotr, & Maes, Michael (2017). Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome.. Molecular neurobiology. https://doi.org/10.1007/s12035-016-9975-2
BibTeX
@article{mecfsatlas-morris-2017-nitrosative-stress,
author = {Morris, Gerwyn and Berk, Michael and Klein, Hans and Walder, Ken and Galecki, Piotr and Maes, Michael},
title = {Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome.},
journal = {Molecular neurobiology},
year = {2017},
doi = {10.1007/s12035-016-9975-2},
note = {PubMed: 27339878},
url = {https://www.mecfsatlas.com/evidence/morris-2017-nitrosative-stress},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/morris-2017-nitrosative-stress
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