Schematic representation of downstream effects of miR-142 upregulation in neurons.

<p>Normally, uninfected neurons have minimal miR-142 expression. Most of the SIRT1 mRNA is therefore available for translation, maintaining the SIRT1 protein pool. SIRT1 deacetylates a lysine residue in the transcription factor NHLH2 and activates it. NHLH2 in turn increases MAOA transcription. In HIVE/SIVE, miR-142 expression is upregulated in neurons. One of the two mature strands of this miR, miR-142-5p, binds to the 3′UTR of SIRT1 mRNA and prevents its translation. This leads to reduction of SIRT1 protein level. Therefore SIRT1 is no longer available for induction if MAOA expression, finally resulting in decrease in MAOA expression and activity.