Affiliations: Center for Cellular Neurobiology and Neurodegeneration Research Department of Biological Sciences University of Massachusetts, Lowell Lowell, MA 01854, USA
Correspondence:
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Corresponding author: Thomas B. Shea, Ph.D., Department of Biological Sciences University of Massachusetts, Lowell Lowell, MA 01854, USA
Abstract: Oxidative stress is thought to be a pivotal factor in Alzheimer's disease (AD). Amyloid-β (Aβ) induces oxidative damage, which is likely to be compounded by deficiencies in endogenous antioxidant capacity. Indeed, folate deprivation, which has been associated with AD, potentiates generation of reactive oxygen species (ROS) by Aβ. We examined whether the antioxidant 17-β-estradiol could attenuate ROS generation following Aβ treatment in the presence and absence of folate using differentiated SH-SY-5Y human neuroblastoma cells. Folate-deprivation and Aβ treatment each induced an increase in ROS, and treatment of folate-deprived cultures with Aβ induced a synergistic increase in ROS. 17-β-estradiol reduced ROS levels in Aβ-treated, folate-deprived cultures to ROS levels observed in cultures treated with Aβ in the presence of folate, suggesting that this antioxidant was able to prevent the synergistic impact of Aβ and folate deprivation on ROS generation. 17-β-estradiol also completely prevented neuronal death induced by both Aβ and folate deprivation individually, and reduced neuronal death following Aβ treatment along with folate deprivation. These findings suggest that therapeutic approaches utilizing antioxidants may be particularly important in conditions such as AD, where multiple factors, including compromises in endogenous antioxidants, promote oxidative stress.
