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bioRxiv · 10.1101/2021.01.27.428475

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

Guisle, I.·Petry, S.·Morin, F.·Kerauden, R.·Whittington, R. A.·Calon, F.·Hebert, S.·Planel, E.
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Abstract

In Alzheimers disease (AD), hyper-phosphorylation and aggregation of tau correlates with clinical progression and represents 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 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.

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Guisle, I., Petry, S., Morin, F., Kerauden, R., Whittington, R. A., Calon, F., Hebert, S., Planel, E.. 2021-01-28. Sauna-like conditions or menthol treatment reduce tau phosphorylation through mild hyperthermia. https://doi.org/10.1101/2021.01.27.428475

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