Fig. 1: Dysfunction of microglia through impaired celluler processes induced by HIV-1 Tat. | Translational Psychiatry

Fig. 1: Dysfunction of microglia through impaired celluler processes induced by HIV-1 Tat.

From: Neuroinflammation and NeuroHIV: understanding the role of HIV-1 related factors in microglial activation

Fig. 1: Dysfunction of microglia through impaired celluler processes induced by HIV-1 Tat.

a HIV Tat-mediated microglial senescence. HIV-1 Tat triggers the miR-505, which negatively regulated the expression of sirtuin(SIRT3). This process may inhibit the expression of antioxidant genes such as manganese superoxide dismutase (MnSOD) and catalase by deacetylating forkhead box O3a (Foxo3a), contributing to mitochondrial oxidative stress and microglial senescence. b HIV Tat-mediated microglial ferroptosis via miR-204-Acyl-CoA synthetase long-chain family member 4 (ACSL4) signaling axis. The upregulation of ACSL4, resulting from the inhibition of miR-204, enhances the synthesis of phospholipid hydroperoxides (PLOOH). Concurrently, the downregulation of glutathione peroxidase-4 (GPX4) exacerbates the accumulation of phospholipid hydroperoxides (PLOOH), supplying fatty acids that promote lipid peroxidation and drive ferroptosis. c HIV Tat-mediated microglial activation by impairing mitophagy. HIV-1 Tat up-regulates mitophagy signaling proteins such as PTEN induced kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PRKN) and dynamin-1-like protein (DNM1L) by decreasing the mitochondrial membrane potential. These processes impair PRKN-dependent mitophagy and the clearance of damaged mitochondria. d HIV Tat-mediated microglial activation by impairing mitophagy. Methamphetamine and HIV-1 Tat induces microglial autophagy via activation of the nuclear factor erythroid-2-related factor 2 (NRF2)/NAD(P)H:quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1) signal pathway.

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