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 A beta(25-35) in vitro. Methods: Isolated rat brain mitochondria were incubated with aged A beta(25-35) for 30 min in the presence and absence of FLZ (1-100 mu mol/L). The activities of key mitochondrial enzymes, the production of hydrogen peroxide (H2O2) and superoxide anion (O-2(-)), 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 A beta(25-35) inhibited the activities of alpha-ketoglutarate dehydrogenase (alpha-KGDH), pyruvate dehydrogenase (PDH) and respiratory chain complex IV. It also resulted in increased H2O2 and O-2(-) 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 mu mol/L) prior to treatment with A beta(25-35) significantly prevented these toxic effects of A beta(25-35) on the mitochondria. Conclusion: FLZ has a protective effect against A beta(25-35) induced mitochondrial dysfunction in vitro.