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Hyperthermia and targeting heat shock proteins: innovative approaches for neurodegenerative disorders and Long COVID

Smadja et al., Frontiers in Neuroscience, doi:10.3389/fnins.2025.1475376, Feb 2025
https://c19early.org/smadja.html
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Review of hyperthermia and heat shock proteins as therapeutic approaches for neurodegenerative disorders and Long COVID. Authors explore how whole-body hyperthermia (WBH) can induce beneficial physiological responses that are difficult to replicate with pharmacological treatments. The paper focuses on how fever-range WBH (38.5-40.5°C) enhances mitochondrial function, induces protective heat shock proteins (HSPs), and modulates neuroinflammation. Authors discuss evidence suggesting WBH may alleviate neurological symptoms in Long COVID, where persistent neuroinflammation and serotonin dysregulation are prominent.
Reviews covering thermotherapy for COVID-19 include1-7.
Smadja et al., 4 Feb 2025, multiple countries, peer-reviewed, 2 authors. Contact: david.smadja@aphp.fr.
Hyperthermia and targeting heat shock proteins: innovative approaches for neurodegenerative disorders and Long COVID
Mario Jose, Patiño Torres, Elena Darmos, Norma Galindo-Sevilla, David M Smadja, M Marc Abreu
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), o ers 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 HSP and HSP 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 e ectsbalancing pro-inflammatory and anti-inflammatory 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 e cacy in NDs and Long COVID. The integration of WBH into therapeutic paradigms could mark a transformative step in addressing these complex conditions.
Author contributions DS: Writing -original draft, Writing -review & editing. MA: Writing -original draft, Writing -review & editing. Conflict of interest MA is founder of BTT medical center. MA is practicing HT however all interpretations and conclusions were drawn independently to ensure objective analysis. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note 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.
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DOI record: { "DOI": "10.3389/fnins.2025.1475376", "ISSN": [ "1662-453X" ], "URL": "http://dx.doi.org/10.3389/fnins.2025.1475376", "abstract": "<jats:p>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 anti-inflammatory 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 integration of WBH into therapeutic paradigms could mark a transformative step in addressing these complex conditions.</jats:p>", "alternative-id": [ "10.3389/fnins.2025.1475376" ], "author": [ { "affiliation": [], "family": "Smadja", "given": "David M.", "sequence": "first" }, { "affiliation": [], "family": "Abreu", "given": "M. Marc", "sequence": "additional" } ], "container-title": "Frontiers in Neuroscience", "container-title-short": "Front. 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