Acta Pharmacologica Sinica (2009) 30: 522-529; doi: 10.1038/aps.2009.45

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 Aβ_25?5 in vitro.

Methods: Isolated rat brain mitochondria were incubated with aged Aβ_25?5 for 30 min 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 Aβ_25?5 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 Aβ_25?5 significantly prevented these toxic effects of Aβ_25?5 on the mitochondria.
                                                                                                                                                                                     
Conclusion: FLZ has a protective effect against Aβ_25?5-induced mitochondrial dysfunction in vitro.
                                                                                                                                                                                                     

Keywords: compound FLZ; β-amyloid; mitochondrial dysfunction; mitochondrial key enzymes; cytochrome c