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.
Highlights
Humans are homeothermic and as such regulate their core body temperature within a narrow range
There are three key points from the scientific literature that support a proposal for a therapeutic effect of heat therapy or heat acclimation to promote heat shock proteins (HSPs) expression in people with neurodegenerative disease
Heat therapy may have additional benefits for muscle function, vasculature health and cerebral blood flow, and indicators of metabolic health, which have been implicated in the pathophysiological presentation of neurodegenerative diseases. These findings from the current scientific literature support the proposal for further investigation into the potentially beneficial adaptations for people with neurodegenerative diseases to heat therapy and heat acclimation
Summary
Humans are homeothermic and as such regulate their core body temperature within a narrow range. HSPs function as chaperones to ensure appropriate cell function with distinct roles in the unfolded protein response, recognizing misfolded or mis-localized proteins that may be subsequently degraded by the proteasome, and are a key component of chaperone-mediated autophagy (Adachi et al, 2009; Stetler et al, 2010; Leak, 2014; Zarouchlioti et al, 2018) For their role in regulating protein homeostasis, HSP expression has been proposed as a therapeutic target for the treatment of these neurodegenerative diseases (Carman et al, 2013; Kalmar et al, 2014; Schapira et al, 2014; Ciechanover and Kwon, 2017; Webster et al, 2017; Klaips et al, 2018). Considerations for undertaking heat acclimation and/or passive heating interventions in people with neurodegenerative diseases will be addressed
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