MicroRNA-101 Regulates Amyloid Precursor Protein Expression in Hippocampal Neurons |
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Authors: | Elisa Vilardo Christian Barbato MariaTeresa Ciotti Carlo Cogoni Francesca Ruberti |
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Institution: | From the ‡INMM-Istituto di Neurobiologia e Medicina Molecolare, CNR, and ;§EBRI-European Brain Research Institute-Fondazione EBRI-Rita Levi-Montalcini, Via del Fosso di Fiorano, 64/65, 00143 Roma, Italy and ;the ¶Dipartimento di Biotecnologie Cellulari ed Ematologia, Università di Roma “La Sapienza”, Viale Regina Elena, 324, 00161 Roma, Italy |
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Abstract: | The amyloid precursor protein (APP) and its proteolytic product amyloid beta (Aβ) are associated with both familial and sporadic forms of Alzheimer disease (AD). Aberrant expression and function of microRNAs has been observed in AD. Here, we show that in rat hippocampal neurons cultured in vitro, the down-regulation of Argonaute-2, a key component of the RNA-induced silencing complex, produced an increase in APP levels. Using site-directed mutagenesis, a microRNA responsive element (RE) for miR-101 was identified in the 3′-untranslated region (UTR) of APP. The inhibition of endogenous miR-101 increased APP levels, whereas lentiviral-mediated miR-101 overexpression significantly reduced APP and Aβ load in hippocampal neurons. In addition, miR-101 contributed to the regulation of APP in response to the proinflammatory cytokine interleukin-1β (IL-lβ). Thus, miR-101 is a negative regulator of APP expression and affects the accumulation of Aβ, suggesting a possible role for miR-101 in neuropathological conditions. |
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Keywords: | Alzheimer Disease Amyloid Gene Regulation MicroRNA Neurobiology APP |
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