کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4325247 | 1613984 | 2012 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: MicroRNA-153 negatively regulates the expression of amyloid precursor protein and amyloid precursor-like protein 2 MicroRNA-153 negatively regulates the expression of amyloid precursor protein and amyloid precursor-like protein 2](/preview/png/4325247.png)
Increased expression of the amyloid precursor protein (APP) is a crucial risk factor of Alzheimer's disease (AD). Amyloid precursor-like protein 2 (APLP2), a homologue of APP, is also suggested to participate in AD pathogenesis. Accumulating evidence suggest the regulatory role of microRNA on AD-related genes. Here we showed that the levels of miR-153 were significantly decreased at early- and late-stage of AD in APPswe/PSΔE9 murine model. Moreover, a binding site of miR-153 on APP and APLP2-3′UTR was identified, respectively, by luciferase assay. Gain and loss of function experiments demonstrated that miR-153 suppressed the expression of APP and APLP2. Using miR-153 transgenic mouse model, we testified that miR-153 downregulated the expression of APP and APLP2 protein in vivo. Furthermore, closely related expression patterns of miR-153 and APP/APLP2 during brain development indicated a physiological regulation role of miR-153 on the two genes. In a neuronal cell line treated with Aβ42 peptides and H2O2, the levels of miR-153 varied during time-course leading to corresponding changes of APLP2 protein, indicating Aβ peptides and oxidative stress influence the expression of miR-153. Thus, miR-153 contributes to post-transcriptional regulation of APP/APLP2, suggesting a possible role for miR-153 in neuro-pathological conditions.
► miR-153 is dysregulated in the brains of APPswe/PSΔE9 mice.
► miR-153 suppresses the expression of APP and APLP2 in vitro and in vivo.
► Aβ peptide and H2O2 influence the expression of miR-153 in cell.
Journal: Brain Research - Volume 1455, 21 May 2012, Pages 103–113