| First Author | Kim J | Year | 2012 |
| Journal | Exp Neurol | Volume | 235 |
| Issue | 2 | Pages | 476-83 |
| PubMed ID | 22119192 | Mgi Jnum | J:187140 |
| Mgi Id | MGI:5435395 | Doi | 10.1016/j.expneurol.2011.11.010 |
| Citation | Kim J, et al. (2012) MiR-106b impairs cholesterol efflux and increases Abeta levels by repressing ABCA1 expression. Exp Neurol 235(2):476-83 |
| abstractText | ATP-binding cassette transporter A1 (ABCA1) is a cholesterol transporter that transfers excess cellular cholesterol onto lipid-poor apolipoproteins. Given its critical role in cholesterol homeostasis, ABCA1 has been studied as a therapeutic target for Alzheimer's disease. Transcriptional regulation of ABCA1 by liver X receptor has been well characterized. However, whether ABCA1 expression is regulated at the posttranscriptional level is largely unknown. Identification of a novel pathway that regulates ABCA1 expression may provide new strategy for regulating cholesterol metabolism and amyloid beta (Abeta) levels. Since ABCA1 has an unusually long 3' untranslated region, we investigated whether microRNAs could regulate ABCA1 expression. We identified miR-106b as a novel regulator of ABCA1 expression and Abeta metabolism. miR-106b significantly decreased ABCA1 levels and impaired cellular cholesterol efflux in neuronal cells. Furthermore, miR-106b dramatically increased levels of secreted Abeta by increasing Abeta production and preventing Abeta clearance. Alterations in Abeta production and clearance were rescued by expression of miR-106b-resistant ABCA1. Taken together, our data suggest that miR-106b affects Abeta metabolism by suppressing ABCA1 expression. |
