Sun, Meng, Zhang, Xinwen, Feng, Xinli et al. · Scientific reports · 2025 · DOI
This study in mice explored how a protein called PKM2 may contribute to ME/CFS by increasing inflammation in the brain and damaging energy-producing structures inside cells (mitochondria). Researchers found that when PKM2 levels increased, cognitive problems worsened and brain cells showed more damage, while reducing PKM2 improved these outcomes. The mechanism involves lactate buildup and activation of inflammatory pathways in the brain.
Understanding the molecular pathways driving ME/CFS is critical for developing targeted treatments. If PKM2-mediated neuroinflammation and mitochondrial damage are confirmed in human patients, inhibiting PKM2 or its downstream signaling could represent a novel therapeutic strategy for cognitive and physical dysfunction in ME/CFS.
This study does not prove that PKM2 dysfunction causes ME/CFS in humans, as it was conducted only in a mouse model with an artificially induced CFS-like state. The findings suggest a potential mechanism but do not establish that human ME/CFS patients have elevated PKM2 activity or that modulating PKM2 would be safe or effective as a treatment. Correlation between PKM2 levels and CFS severity in patients remains undemonstrated.
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
Sun, Meng, Zhang, Xinwen, Feng, Xinli, & Liang, Lu (2025). PKM2 accelerated the progression of chronic fatigue syndrome via promoting the H4K12la/ NF-κB induced neuroinflammation and mitochondrial damage.. Scientific reports. https://doi.org/10.1038/s41598-025-93313-w
BibTeX
@article{mecfsatlas-sun-2025-pkm2-accelerated,
author = {Sun, Meng and Zhang, Xinwen and Feng, Xinli and Liang, Lu},
title = {PKM2 accelerated the progression of chronic fatigue syndrome via promoting the H4K12la/ NF-κB induced neuroinflammation and mitochondrial damage.},
journal = {Scientific reports},
year = {2025},
doi = {10.1038/s41598-025-93313-w},
note = {PubMed: 40155479},
url = {https://www.mecfsatlas.com/evidence/sun-2025-pkm2-accelerated},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/sun-2025-pkm2-accelerated
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