Durham Research Center 8034
985880 Nebraska Medical Center
Omaha, NE 68198-5880
Email: Jianuo Liu
Keywords: HIV-1 associated neurological disorders
The long-term goal of my research is to determine and identify potential target(s) for the development of therapeutic strategies that may tackle microglia neurotoxic activity and enhance neuronal function and survival in HIV-1 associated neurocognitive disorders.
HIV/AIDS has been a serious global problem with huge social, health, and economic consequences. Currently, approximately 40 million people worldwide are infected with HIV-1 and 20-40% of these patients develop HIV-1-associated neurocognitive disorders (HAND), characterized by a syndrome of progressive cognitive, behavioral, and neurological impairments. Despite the widespread use of antiretroviral therapy (ART), the incidence of HAND continues to have devastating impact on the population. This is mainly due to an incomplete understanding of how HIV infection causes neuronal injury and apoptosis, leading to cognitive disorder. Therefore, my research focus is to study how HIV-1 brain infection alters brain macrophage and microglia functions leading to HIV-1-associated neurocognitive impairments.
1: Role of potassium (KV) channels in HIV-1 protein (gp120, Tat)-induced microglia neurotoxicity. Microglia are the primary immune cells in the central nervous system and activated microglia produce soluble factors leading to neuronal injury. Recently, voltage-gated KV channels have gained attention as promising targets for development of therapeutic strategies. Thus, we use molecular immunology and physiology techniques to explore whether KV channels are involved in HIV-1 protein including gp120 and Tat-induced microglia neuronal toxicity. Our findings implicate that HIV-1 proteins (gp120 and Tat) enhanced microglia KV channel expressions, especially KV1.3, leading to microglia activation and resultant production of neurotoxins and consequent neuronal injury. Enhancement of microglia KV1.3 current is mediated through MAPK pathway including Erk1/2 and p38. Blockage of KV1.3 expression attenuated neurotoxicity induced by gp120- or Tat-activated microglia. These results suggest that KV1.3 channel may be a promising target to a new avenue of therapy for immune and inflammation-mediated neurological disorders.
2: Co-morbid effects of HIV-1 infection and drug abuse. Drug abuse is a major cause of the spread of HIV/AIDS. Studies have shown that the incidence and severity of HIV-associated neurocognitive disorders (HAND) are increased with concomitant use of Meth. In this study, we are actively pursuing how Meth synergizes with HIV-1 gp120 protein to exacerbate HAND. Our data indicate that Meth and HIV activate microglia resulting in microglia production of neurotoxins and consequent neural injury, suggesting microglia appears to be the intersecting target and effector of the two. In addition, the voltage-gated KV channels are also involved in modulating microglia neurotoxic activity. Specifically, this Meth and HIV act synergistically on microglia is controlled by caspase signal pathway.
- Liu H, Liu J, Liang S, Xiong H. (2013) Plasma gelsolin protects HIV-1 gp120-Induced neuronal injury via voltage-gated K+ channel Kv2.1. Mol cell Neurosci S1044-7431: 00101-2. PMID: 24513395
- Xiong W, Xie J, Liu J, Xiong H. (2014) [HIV-1gp120 injures neurons by alteration of neuronal expressions of NR2B and PSD-95]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 30(2): 139-42. PMID: 24491052
- Liu H, Liu J, Liang S, Xiong H. (2013) Plasma gelsolin protects HIV-1 gp120-induced neuronal injury via voltage-gated K+ channel Kv2.1. Mol Cell Neurosci 57:73-82. PMID: 24416794
- Liu J, Xu P, Collins C, Liu H, Zhang J, Keblesh JP, Xiong H. (2013) HIV-1 Tat protein increases microglial outward K(+) current and resultant neurotoxic activity. PLoS One 8(5): e64904. PMID: 23738010
- Yang J, Hu D, Xia J, Liu J, Zhang G, Gendelman HE, Boukli NM, Xiong H. (2013) Enhancement of NMDA receptor-mediated excitatory postsynaptic currents by gp120-treated macrophages: implications for HIV-1-associated neuropathology. J Neuroimmune Pharmacol 8(4): 921-33. PMID: 23660833
- Zhang J, Liu J, Fox HS, Xiong H. (2013) N-methyl-D-aspartate receptor-mediated axonal injury in adult rat corpus callosum. J Neurosci Res 91(2): 240-8. PMID: 23161705
- Chen L, Liu J, Xu C, Keblesh J, Zang W, Xiong H. (2011) HIV-1gp120 induces neuronal apoptosis through enhancement of 4-aminopyridine-senstive outward K+ currents. PLoS 6(10): e25994. PMID: 22016798
- Xu C, Liu J, Chen L, Liang S, Fujii N, Tamamura H, Xiong H. (2011) HIV-1 gp120 enhances outward potassium current via CXCR4 and cAMP-dependent protein kinase A signaling in cultured rat microglia. Glia 59(6): 997-1007. PMID: 21438014
- Zhang J, Liu J, Katafiasz B, Fox H, Xiong H. (2011) HIV-1 gp120-induced axonal injury detected by accumulation of β-amyloid precursor protein in adult rat corpus callosum. J Neuroimmune Pharmacol 6(4): 650-7. PMID: 21286834
- Zhou Y, Tang H, Liu J, Dong J, Xiong H. (2011) Chemokine CCL2 modulation of neuronal excitability and synaptic transmission in rat hippocampal slices. J Neurochem 116(3): 406-14. PMID: 21105875
Additional publications in PubMed.