Protective effects of compound FLZ,a novel synthetic analogue of squamosamide,on β-amyloid-induced rat brain mitochondrial dysfunction in vitro

Aim： The aim of the present study was to assess the effects of N-[2-（4-hydroxyphenyl）ethyl]-2-（2,5-dimethoxyphenyl）-3-（3- methoxy-4-hydroxyphenyl） acrylamide （compound FLZ）, a novel synthetic analogue of squamosamide, on the dysfunction of rat brain mitochondria induced by Aβ25-35 in vitro. Methods： Isolated rat brain mitochondria were incubated with aged Aβ25-35 for 30 rain in the presence and absence of FLZ （1-100 μmol/L）. The activities of.key mitochondrial enzymes, the production of hydrogen peroxide （H2O2） and superoxide anion （O2^-）, and the levels of glutathione （GSH） in mitochondria were examined. Mitochondrial swelling and the release of cytochrome c from mitochondria were assessed by biochemical and Western blot methods, respectively. Results： Incubation of mitochondria with aged Aβ25-35 inhibited the activities of α-ketoglutarate dehydrogenase （α-KGDH）, pyruvate dehydrogenase （PDH） and respiratory chain complex IV. It also resulted in increased H2O2 and O2^- production, and decreased the GSH level in mitochondria. Furthermore, it induced mitochondrial swelling and cytochrome c release from the mitochondria. The addition of FLZ （100 μmol/L） prior to treatment with Aβ25-35 significantly prevented these toxic effects of Aβ25-35 on the mitochondria. Conclusion： FLZ has a protective effect against Aβ25-35-induced mitochondrial dysfunction in vitro.