Thermal cycling-hyperthermia attenuates rotenone-induced cell injury in SH-SY5Y cells through heat-activated mechanisms
Parkinson's 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 reduced ROT-induced mitochondrial apoptosis and ROS accumulation in SH-SY5Y cells. 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, which can be practically implemented via the focused ultrasound (FUS).