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. 2022 May:113:118-130.
doi: 10.1016/j.neurobiolaging.2022.02.011. Epub 2022 Feb 26.

Sauna-like conditions or menthol treatment reduce tau phosphorylation through mild hyperthermia

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Sauna-like conditions or menthol treatment reduce tau phosphorylation through mild hyperthermia

Isabelle Guisle et al. Neurobiol Aging. 2022 May.

Abstract

In Alzheimer's disease (AD), hyper-phosphorylation and aggregation of tau correlate with clinical progression and represent a valid therapeutic target. A recent 20-year prospective study revealed an association between moderate to high frequency of Finnish sauna bathing and a lower incidence of dementia and AD, but the molecular mechanisms underlying these benefits remain uncertain. Here, we tested the hypothesis that sauna-like conditions could lower tau phosphorylation by increasing body temperature. We observed a decrease in tau phosphorylation in wild-type and hTau mice as well as in neuron-like cells when exposed to higher temperatures. These effects were correlated with specific changes in phosphatase and kinase activities, but not with inflammatory or heat shock responses. We also used a drug strategy to promote thermogenesis: topical application of menthol, which led to a sustained increase in body temperature in hTau mice, concomitant with a significant decrease in tau phosphorylation. Our results suggest that sauna-like conditions or menthol treatment could lower tau pathology through mild hyperthermia, and may provide promising therapeutic strategies for AD and other tauopathies.

Keywords: Alzheimer's disease; Hyperthermia; Menthol; Sauna bathing; Tau protein phosphorylation; Thermogenesis.

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