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Neuroprotective actions of DHEA and DHEAS in primary mouse neurons and SH-SY5Y cells exposed to toxic amyloid beta oligomers

Introduction: Alzheimer´s disease (AD) is neurodegenerative disease characterized by cognitive impairment and progressive synaptic damage accompanied by neuronal loss. The causes of amyloid beta aggregation that form amyloid plaques in the pathogenesis of AD has been debated for more than 25 years and it is supposed that amyloid beta oligomers may be the toxic factors acting on a very early stage of AD. Currently available therapy provides only symptomatic treatment, while many studies of new effective drugs have so far been unsuccessful. Therefore, neurosteroids dehydroepiandrosterone (DHEA) and its sulfated form dehydroepiandrosterone sulfate (DHEAS) are of a great interest due to their potential to modulate neurogenesis, neuronal growth and differentiation, as well as neuroprotection. Materials and methods: Neuroprotective effects of DHEA and DHEAS were investigated using primary mouse neurons, isolated from C57BL/6 mice embryos, and human SH-SY5Y neuroblastoma cells simultaneously exposed to toxic amyloid beta oligomers during 24 hours. Various assays (MTT, Muse, Promega) were used to determine cell viability and underlying mechanisms, while GraphPad Prism was used to interpret the obtained results. Results: Our results demonstrated that DHEA and DHEAS exert neuroprotective actions on primary mouse neurons and SH-SY5Y cells exposed to amyloid beta oligomers, probably via anti-apoptotic mechanisms. Conclusions: These findings suggest that DHEA and DHEAS may have therapeutic effects against amyloid beta toxicity. DHEA(S) could potentially represent novel preventive and/or therapeutic agents for AD in the future. This study needs to be confirmed and extended by further in vitro research and studies using animal models and human samples.

DHEA ; DHEAS ; BDNF ; Alzheimer´s disease ; amyloid beta aggregation

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