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bioRxiv · 10.1101/2025.03.12.642756

Thermal cycling-hyperthermia attenuates rotenone-induced cell injury in SH-SY5Y cells through heat-activated mechanisms

Kuo, Y.-Y.·Lin, G.-B.·Chen, Y.-M.·Liu, H.-H.·Hsu, F.-T.·Kung, Y.·Chao, C.-Y.
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Abstract

Parkinsons disease (PD) is the second most prevalent neurodegenerative disease. It is characterized by mitochondrial dysfunction, increased reactive oxygen species (ROS), -synuclein (-syn) and phosphorylated-tau protein (p-tau) aggregation, and dopaminergic neuron cell death. Current drug therapies only provide temporary symptomatic relief and fail to stop or reverse disease progression due to the severe side effects or the blood-brain barrier. This study aimed to investigate the neuroprotective effects of thermal cycling-hyperthermia (TC-HT) in an in vitro PD model using rotenone (ROT)-induced human neural SH-SY5Y cells. Our results revealed that TC-HT pretreatment conferred neuroprotective effects in the ROT-induced in vitro PD model using human SH-SY5Y neuronal cells, including reducing ROT-induced mitochondrial apoptosis and ROS accumulation in SH-SY5Y cells. In addition, TC-HT also inhibited the expression of -syn and p-tau through heat-activated pathways associated with sirtuin 1 (SIRT1) and heat-shock protein 70 (Hsp70), involved in protein chaperoning, and resulted in the phosphorylation of Akt and glycogen synthase kinase-3{beta} (GSK-3{beta}), which inhibit p-tau formation. These findings underscore the potential of TC-HT as an effective treatment for PD in vitro, supporting its further investigation in in vivo models or potentially in human trials, with focused ultrasound (FUS) as a feasible heat-delivery approach.

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Kuo, Y.-Y., Lin, G.-B., Chen, Y.-M., Liu, H.-H., Hsu, F.-T., Kung, Y., Chao, C.-Y.. 2025-03-13. Thermal cycling-hyperthermia attenuates rotenone-induced cell injury in SH-SY5Y cells through heat-activated mechanisms. https://doi.org/10.1101/2025.03.12.642756

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