Thermal cycling protects SH-SY5Y cells against hydrogen peroxide and β-amyloid-induced cell injury through stress response mechanisms involving Akt pathway

Abstract

<jats:title>Abstract</jats:title><jats:p>Neurodegenerative diseases (NDDs) are becoming a major threat to public health, according to the World Health Organization (WHO). The most common form of NDDs is Alzheimer’s disease (AD), boasting 60-70% share. Excessive aggregation of β-amyloid protein (Aβ) and neurofibrillary tangles has been deemed the major cause for the pathogenesis of AD. A growing number of evidences from studies, however, have suggested that reactive oxygen species (ROS) also play a key role in the onset and progression of AD. Although scientists have had some understanding of the pathogenesis of AD, the disease still cannot be cured, with existing treatment only capable of providing a temporary relief at best, partly due to the obstacle of blood-brain barrier (BBB). The study was aimed to ascertain the neuroprotective effect of thermal cycle hyperthermia (TC-HT) against hydrogen peroxide (H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>) and Aβ-induced cytotoxicity in SH-SY5Y cells. Treating cells with this physical stimulation beforehand significantly improved the cell viability and decreased the ROS content. The underlying mechanisms were confirmed to be due to the activation of Akt pathway and the downstream antioxidant and prosurvival proteins. The findings manifest significant potential of TC-HT in neuroprotection, via inhibition of oxidative stress and cell apoptosis. It is believed that coupled with the use of drugs or natural compounds, this methodology can be even more effective in treating NDDs.</jats:p>

Thermal cycling-hyperthermia ameliorates cognitive impairment of intracerebroventricular Aβ25-35-induced Alzheimer’s disease in C57BL/6 mice

“…As shown in Fig 7A , the result shows significant recovery of the Aβ-inhibited viability of SH-SY5Y cells after TC-HT treatment, whose neuroprotective effect could be attributed to activation of Akt and its downstream signalling pathways, as suggested in our previous study [32]. It has been reported that early administration of antioxidants may block the construction of neuroprotection via these pathways [61][62][63], which is in Overall, the study validates the therapeutic potential of TC-HT for AD in vivo, shedding light on development of alternative AD treatment with high efficacy.…”

“…Development of AD drugs has been confronted with two major obstacles, namely blood-brain barrier (BBB) and severe side effects [14,46]. Hence, the application of heat has potential as an alternative AD treatment, due to its capability to intensify neuroprotective effect [32] and sidestep BBB, targeting the diseased brain directly.…”

“…The study embraced TC-HT, a modified heat treatment with higher safety and superior protective effect than HT [32], to investigate the therapeutic potential of thermal treatment on AD in vivo.…”

“…The study applied TC-HT to treat mice with AD, induced by intracerebroventricular (i.c.v.) injection of Aβ [25][26][27][28][29][30][31][32][33][34][35] , for comparison with the therapeutic effect of HT. In both cases, heat was applied to mouse brain specifically, to avoid potential side effect of whole-body HT.…”

The key roles of organelles and ferroptosis in Alzheimerʼs disease

“…Alzheimerʼs disease (AD), a neurodegenerative disease closely related to age, is characterized by progressive degeneration and neuronal necrosis, leading to memory loss, cognitive impairment, and behavioral impairment (Chen et al, 2020; Martins et al, 2019). As the global population ages, AD is becoming increasingly common, causing great harm to patients and their families, and becoming a global health concern.…”