Therapeutic effects of Ginkgo biloba extract EGB 761 in animal models of Alzheimer’s disease

assessed for mitochondrial respiratory activity and enzymatic activity in the presence and absence of toxic calcium exposure. Primary hippocampal rat neurons exposed to E2 or vehicle control were assessed for cytochrome c release and Bax translocation by immunocytochemistry and western blot analysis. Conclusions: E2-treated mitochondria displayed enhanced respiratory function coupled to increased expression and activity of the electron transport chain complex IV (cytochrome c oxidase). This enhancement of basal mitochondrial function was paralleled by the neuroprotective effects of E2, which were evidenced by an attenuation of the calcium-induced decline in mitochondrial respiratory function. Apoptosis during neurodegeneration is preceded by release of cytochrome c from the mitochondrial intermembrane space. This translocation is regulated by the expression and localization of the Bcl-2 family of proteins. We showed that E2 prevents the glutamateand A-induced reciprocal mitochondrial/cytosolic translocation of cytochrome c and Bax. These data suggest a mechanism of E2 neuroprotection involving an increase in Ca sequestration by mitochondria coupled with an increase in mitochondrial Ca load tolerability and an increase in mitochondrial respiratory function.