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REVIEW article

Front. Neurosci.
Sec. Neurodegeneration
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1475376
This article is part of the Research Topic Neuropsychiatric Consequences of the COVID-19 Pandemic: Understanding Mechanisms, Risk Factors, and Treatment View all 4 articles

Hyperthermia and targeting heat shock proteins: Innovative Approaches for Neurodegenerative Disorders and Long COVID

Provisionally accepted
David M SMADJA David M SMADJA 1,2*M Marc Abreu M Marc Abreu 3
  • 1 Hematology, Université Paris Cité, Paris, France
  • 2 Service d'Hématologie, Hôpital Européen Georges Pompidou, Paris, France
  • 3 BTT Medical Center, Aventura, United States

The final, formatted version of the article will be published soon.

    Neurodegenerative diseases (NDs) and Long COVID represent critical and growing global health challenges, characterized by complex pathophysiological mechanisms including neuronal deterioration, protein misfolding, and persistent neuroinflammation. The emergence of innovative therapeutic approaches, such as whole-body hyperthermia (WBH), offers promising potential to modulate underlying pathophysiological mechanisms in NDs and related conditions like Long COVID. WBH, particularly in fever-range, enhances mitochondrial function, induces heat shock proteins (HSPs), and modulates neuroinflammation-benefits that pharmacological treatments often struggle to replicate. HSPs such as HSP70 and HSP90 play pivotal roles in protein folding, aggregation prevention, and cellular protection, directly targeting pathological processes seen in NDs like Alzheimer's, Parkinson's, and Huntington's disease. Preliminary findings also suggest WBH's potential to alleviate neurological symptoms in Long COVID, where persistent neuroinflammation and serotonin dysregulation are prominent. Despite the absence of robust clinical trials, the therapeutic implications of WBH extend to immune modulation and the restoration of disrupted physiological pathways. However, the dual nature of hyperthermia's effects-balancing pro-inflammatory and antiinflammatory responses-emphasizes the need for dose-controlled applications and stringent patient monitoring to minimize risks in vulnerable populations. While WBH shows potential interest, significant challenges remain. These include individual variability in response, limited accessibility to advanced hyperthermia technologies, and the need for standardized clinical protocols. Future research must focus on targeted clinical trials, biomarker identification, and personalized treatment strategies to optimize WBH's efficacy in NDs and Long COVID. The 9 3 integration of WBH into therapeutic paradigms could mark a transformative step in addressing 41 these complex conditions. 42 9 4

    Keywords: hyperthermia, Neurodegenerative disorders, Serotonin, Long Covid, heat shock

    Received: 03 Aug 2024; Accepted: 03 Jan 2025.

    Copyright: © 2025 SMADJA and Abreu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: David M SMADJA, Hematology, Université Paris Cité, Paris, 75006, France

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.