Dopaminergic neurotransmission is reduced in advanced stages of the AbMole Butylhydroxyanisole disease as evidenced by reduction in dopamine levels in post-mortem brain and CSF samples. This may be a result of progressive loss of dopaminergic neurons in the brain. However, 
in early stages of the disease, an increase in dopaminergic tone has been observed. Treatment na? ��ve asymptomatic HIV patients have higher levels of dopamine in the CSF due to decrease in dopamine turnover, as evidenced by lower CSF levels of the dopamine metabolite, homovallinic acid. This suggests a possible decrease in activity of dopamine-catabolizing enzymes, such as MAO and Catechol-O-Methyl Transferase, early in the disease. Upregulation of miR-142 may contribute to such changes in dopaminergic neurotransmission in the disease by lowering MAOA expression and activity. Although miR-142 expressing cells had lower MAOA expression and activity, miR-142 cannot target MAOA directly as there are no miR-142 recognition elements in the MAOA 39UTR. Therefore regulation of MAOA by miR-142 must be AbMole Nitroprusside disodium dihydrate mediated by a direct miR-142 target. In this context, the NAD-dependent deacetylase SIRT1, was reported to regulate transcription of MAOA. SIRT1 deacetylates and activates the transcription factor NHLH2, inducing MAOA expression. SIRT1 is also a validated target for miR-142-5p. Cells that express high levels of miR-142 in SIVE have lower SIRT1 protein levels. Decrease in SIRT1 levels due to upregulation of miR-142 could therefore explain this decrease in MAOA expression and activity. Indeed, we found that overexpression of SIRT1 in the BEM17 clones could increase MAOA protein level. In addition to neurons, upregulation of miR-142 was also observed in myeloid cells in the SIVE brain. Recent studies have demonstrated that myeloid cells express components of the dopaminergic system including dopamine receptors, dopamine transporters and the dopamine synthesizing enzyme tyrosine hydroxylase. MAOA is also expressed in monocytes/ macrophages where it is strongly induced by the Th2 cytokines IL4 and IL-13; although its function in these cell types is not clear it is speculated that it serves an immunomodulatory role. Further investigation is therefore required to elucidate the functional effect of upregulation of miR-142 and downregulation of MAOA in microglia/macrophages in SIVE. In conclusion, we found that chronic increase in neuronal miR142 expression leads to decrease in MAOA expression and activity. This effect of miR-142 on MAOA expression level is mediated by downregulation of the direct miR-142-5p target SIRT1. Upregulation of miR-142 may therefore contribute to changes in dopaminergic neurotransmission reported in HAND. The renal medullary interstitial cells are a population of specialized stroma-like cells in renal medulla.