کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3070251 | 1580724 | 2008 | 9 صفحه PDF | دانلود رایگان |
In this study, we tested if caspase-3 inhibition decreased ischemia-induced Aβ elevation by reducing β-secretase (BACE1) activity. Changes in caspase-3, Aβ 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, Aβ, 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 Aβ 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 Aβ formation by reducing BACE1 production and activity. This finding provides a therapeutic strategy for preventing Aβ accumulation and reducing the risk of neurodegeneration after stroke.
Journal: Neurobiology of Disease - Volume 32, Issue 3, December 2008, Pages 433–441