Hyperthermia and targeting heat shock proteins: innovative approaches for neurodegenerative disorders and Long COVID
Summary & key facts
This paper reviews early evidence that raising body temperature in a controlled way — called whole-body hyperthermia — may affect brain problems seen in diseases like Alzheimer's, Parkinson's, Huntington's and in some cases of Long COVID. Heating the body to fever-like levels can boost special protective proteins (heat shock proteins), improve how cells' energy makers (mitochondria) work, and change brain inflammation. These effects could lower harmful protein clumping and protect nerve cells. But solid clinical trials are missing, and heating can cause both helpful and harmful immune reactions, so careful control and more research are needed before this approach can be used widely.
- Whole-body hyperthermia at fever-like temperatures can increase heat shock proteins such as HSP70 and HSP90, which are proteins that help other proteins fold correctly and avoid clumping.
- Raising body temperature in this way also seems to improve mitochondrial function, meaning the cell parts that make energy may work better after controlled heating.
- Heat shock proteins and improved mitochondrial function target problems that are common in neurodegenerative diseases, like misfolded proteins and damaged nerve cells, seen in Alzheimer's, Parkinson's, and Huntington's disease.
- Some early findings suggest whole-body hyperthermia might reduce neurological symptoms in people with Long COVID, possibly by lowering persistent brain inflammation and affecting serotonin balance, but this evidence is preliminary.
- Hyperthermia can trigger both pro-inflammatory and anti-inflammatory effects, so it needs precise doses and close patient monitoring to avoid harm, especially in vulnerable people.
- There are few robust clinical trials and few standardized methods now, so researchers say we need targeted trials, reliable biological markers, and personalized treatment plans before hyperthermia can be adopted clinically.
Abstract
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.