Fronticelli Baldelli, Giovanni, Buonsenso, Danilo · Children (Basel, Switzerland) · 2025 · DOI
This review proposes that a protein called mTOR may be the key link between infections and the long-lasting symptoms seen in ME/CFS and similar post-infection illnesses. The authors suggest that when mTOR stays overactive after an infection, it can damage the barrier that protects the brain, allow immune cells to enter brain tissue, and cause ongoing inflammation that affects how the brain works. They outline a step-by-step pathway explaining how this might happen and suggest that targeting mTOR could be a new treatment approach.
Understanding the mechanism underlying ME/CFS is critical for developing effective treatments. This framework offers a testable hypothesis that could explain why infections trigger prolonged neurological and immunological symptoms in ME/CFS patients and suggests potential therapeutic targets—such as mTOR inhibitors—that could be investigated in clinical trials.
This is a hypothesis-generating review based on existing literature, not original experimental data. It does not prove that mTOR hyperactivation causes ME/CFS or that mTOR inhibitors will be effective treatments. The proposed pathway requires empirical validation through direct measurement of mTOR activity, barrier permeability, and immune markers in ME/CFS patients.
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 →
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Primary citation
Fronticelli Baldelli, Giovanni & Buonsenso, Danilo (2025). Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.. Children (Basel, Switzerland). https://doi.org/10.3390/children12121603
BibTeX
@article{mecfsatlas-fronticelli-baldelli-2025-proposed-mechanistic,
author = {Fronticelli Baldelli, Giovanni and Buonsenso, Danilo},
title = {Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.},
journal = {Children (Basel, Switzerland)},
year = {2025},
doi = {10.3390/children12121603},
note = {PubMed: 41462744},
url = {https://www.mecfsatlas.com/evidence/fronticelli-baldelli-2025-proposed-mechanistic},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/fronticelli-baldelli-2025-proposed-mechanistic
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