Andrew P. Hunt1,2*, Geoffrey M. Minett1,2, Oliver R. Gibson3,4, Graham K. Kerr1,2 and Ian B. Stewart1,2
- 1School of Exercise and Nutrition Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia
- 2Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
- 3Centre for Human Performance, Exercise and Rehabilitation, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom
- 4Division of Sport, Health and Exercise Sciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom
ABSTRACT
Neurodegenerative diseases involve the progressive deterioration of structures within the central nervous system responsible for motor control, cognition, and autonomic function. Alzheimer’s disease and Parkinson’s disease are among the most common neurodegenerative disease and have an increasing prevalence over the age of 50. Central in the pathophysiology of these neurodegenerative diseases is the loss of protein homeostasis, resulting in misfolding and aggregation of damaged proteins. An element of the protein homeostasis network that prevents the dysregulation associated with neurodegeneration is the role of molecular chaperones. Heat shock proteins (HSPs) are chaperones that regulate the aggregation and disaggregation of proteins in intracellular and extracellular spaces, and evidence supports their protective effect against protein aggregation common to neurodegenerative diseases. Consequently, upregulation of HSPs, such as HSP70, may be a target for therapeutic intervention for protection against neurodegeneration. A novel therapeutic intervention to increase the expression of HSP may be found in heat therapy and/or heat acclimation. In healthy populations, these interventions have been shown to increase HSP expression. Elevated HSP may have central therapeutic effects, preventing or reducing the toxicity of protein aggregation, and/or peripherally by enhancing neuromuscular function. Broader physiological responses to heat therapy have also been identified and include improvements in muscle function, cerebral blood flow, and markers of metabolic health. These outcomes may also have a significant benefit for people with neurodegenerative disease. While there is limited research into body warming in patient populations, regular passive heating (sauna bathing) has been associated with a reduced risk of developing neurodegenerative disease. Therefore, the emerging evidence is compelling and warrants further investigation of the potential benefits of heat acclimation and passive heat therapy for sufferers of neurodegenerative diseases.
INTRODUCTION
Humans are homeothermic and as such regulate their core body temperature within a narrow range. Perturbations to this homeostasis, induced by external environmental thermal stress or internally generated metabolic heat, produces both autonomic and behavioral responses designed to elicit a return of core body temperature toward thermal balance (Schlader and Vargas, 2019). While in an acute sense this stress response is a defense mechanism, regularly challenging the thermal equilibrium via active or passive thermal stress results in positive physiological and perceptual adaptations (Tyler et al., 2016). Recent research has shown positive therapeutic effects of passive heating for people with peripheral arterial disease (Neff et al., 2016; Akerman et al., 2019), chronic heart failure (Kihara et al., 2002; Ohori et al., 2012), diabetes (Hooper, 1999), and depression (Janssen et al., 2016). Passive heating also improves a range of health markers, including cardiovascular health indices, such as vascular function, blood pressure, and arterial stiffness (Brunt et al., 2016a, b), as well as metabolic health and glycemic control (Janssen et al., 2016; Kimball et al., 2018; Ely et al., 2019; Maley et al., 2019). Several mechanistic pathways may underpin these adaptations, including improved cellular respiration (Hafen et al., 2018), circulating factors (Brunt et al., 2019), and vascular shear stress (Tinken et al., 2009; Thomas et al., 2016). The upregulation of heat shock proteins (HSPs) as a result of acute and/or chronic (repeated) exposure to passive heating is also an adaptive outcome, which may provide a specific mechanistic pathway for improving health and function within the body (Faulkner et al., 2017; Brunt et al., 2018).