MicroRNA-101 regulates amyloid precursor protein expression in hippocampal neurons.
The amyloid precursor protein (APP) and its proteolytic product amyloid beta (Abeta) 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 Abeta load in hippocampal neurons. In addition, miR-101 contributed to the regulation of APP in response to the proinflammatory cytokine interleukin-1beta (IL-lbeta). Thus, miR-101 is a negative regulator of APP expression and affects the accumulation of Abeta, suggesting a possible role for miR-101 in neuropathological conditions.
Vilardo
Elisa
E
Istituto di Neurobiologia e Medicina Molecolare, CNR, Roma, Italy.
Barbato
Christian
C
Ciotti
Mariateresa
M
Cogoni
Carlo
C
Ruberti
Francesca
F
D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D000818:Animals; D060565:Argonaute Proteins; D001483:Base Sequence; D001921:Brain / Q000196:embryology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006624:Hippocampus / Q000196:embryology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
C582332:Ago2 protein, rat; D016564:Amyloid beta-Protein Precursor; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D053583:Interleukin-1beta; C534072:MIRN101 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs
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