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Title: Caspase inhibition attenuates accumulation of beta-amyloid by reducing beta-secretase production and activity in rat brains after stroke. Author: Xiong M, Zhang T, Zhang LM, Lu SD, Huang YL, Sun FY. Journal: Neurobiol Dis; 2008 Dec; 32(3):433-41. PubMed ID: 18805488. Abstract: In this study, we tested if caspase-3 inhibition decreased ischemia-induced Abeta elevation by reducing beta-secretase (BACE1) activity. Changes in caspase-3, Abeta and BACE1 levels were detected in rat striatum on different days after middle cerebral artery occlusion using immunostaining. We found that the positive labeled cells of activated caspase-3, Abeta, and BACE1 were significantly and time-dependently increased in the ipsilateral striatum. The results of Western blotting and RT-PCR showed that caspase-3 inhibitor Z-DEVD-FMK reduced BACE1 mRNA and protein levels, and inhibited its protease activity, thereby decreasing the amount of APP C99 and Abeta in ischemic brains. Moreover, Z-DEVD-FMK reduced BACE1 and GFAP double-labeled cells, but not GFAP protein levels or GFAP-labeled cells, in the ipsilateral striatum. Thus, we demonstrated that caspase-3 inhibition attenuated ischemia-induced Abeta formation by reducing BACE1 production and activity. This finding provides a therapeutic strategy for preventing Abeta accumulation and reducing the risk of neurodegeneration after stroke.[Abstract] [Full Text] [Related] [New Search]