Anat Elmann
Agricultural Research Organization, Austria
Title: Harnessing phytochemicals to protect neuronal and glial cells from oxidative stress
Biography
Biography: Anat Elmann
Abstract
Oxidative stress and amyloid beta toxicity are involved in the pathogenesis of Alzheimer's diseases. We have previously demonstrated
that an extract prepared of the plant Achillea fragrantissima (Af) protected cultured brain astrocytes from oxidative stressinduced
cell death and down regulated microglial activation. Using activity guided fractionation, we have purified from Af an active
flavonoid named 3,5,4-trihydroxy-6,7,3-trimethoxyflavone (TTF). TTF protected cultured astrocytes from H2O2–induced cell death
via interference with cell signaling (inhibition of SAPK/JNK, ERK 1/2, and MEK1 phosphorylation) and by reducing the levels of
oxidative stress-induced intracellular reactive oxygen species (ROS). The mechanism of the protective effect of TTF against H2O2-
cytotoxicity could not be attributed to a direct H2O2 scavenging but rather to the scavenging of free radicals as was shown in cell free
systems. In addition, TTF protected cultured neuronal cells from amyloid beta cytotoxicity via interference with cell signaling events
and by reducing the amyloid beta - induced levels of intracellular ROS. Moreover, TTF exhibited anti-inflammatory activities and
inhibited the LPS-elicited secretion of the proinflammatory cytokines Interleukin 6 (IL-6) and IL-1beta from microglial cells. Our
results suggest that TTF might be a therapeutic candidate for the treatment of Alzheimer’s disease as well as other neurodegenerative
diseases where oxidative stress, neuroinflammation and amyloid beta toxicity are part of the pathophysiology.
aelmann@volcani.agri.gov.il