Human immunodeficiency virus type-1 protein Tat induces tumor necrosis factor-α-mediated neurotoxicity

Buscemi, Lara; Ramonet, David; Geiger, Jonathan D.

doi:10.1016/j.nbd.2007.03.004

Cited by 65 publications

(63 citation statements)

References 77 publications

(102 reference statements)

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“…There is no conclusive evidence of direct neuronal infection by HIV-1, and the decreased cell proliferation of NPSc or neuronal death is considered to be a consequence of the toxic effects of viral and cellular neurotoxins that are released from virus-infected and/or activated cells (Eugenin et al 2003; Mishra et al 2010). Among the viral products, HIV Tat has been shown to be neuroexcitatory and neurotoxic, and it continues to be implicated as a causative agent in HAND (Buscemi et al 2007; Agrawal et al 2012). Tat can be both secreted from infected cells and can also be taken up by neighboring non-infected cells, including neurons (Liu et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Platelet-Derived Growth Factor-BB Restores HIV Tat -Mediated Impairment of Neurogenesis: Role of GSK-3β/β-Catenin

Chao

Lü

Yao

et al. 2013

J Neuroimmune Pharmacol

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Our previous study demonstrated that platelet-derived growth factor-BB (PDGF-BB) increased the cell proliferation of primary rat neuronal progenitor cells (NPCs). However, whether PDGF-BB regulates neurogenesis in HIV-associated neurological disorder (HAND) remains largely unknown. In this study we demonstrated that pre-treatment of NPCs with PDGF-BB restored Tat-mediated impairment of cell proliferation via activation of p38 and JNK MAPK pathways. Moreover, treatment with PDGF-BB induced inactivation of glycogen synthase kinase-3β (GSK-3β), evidenced by its phosphorylation at Ser9, this effect was significantly inhibited by the p38 and JNK inhibitors. Level of nuclear β-catenin, the primary substrate of GSK-3β, was also concomitantly increased following PDGF-BB treatment, suggesting that PDGF-BB stimulates NPC proliferation via acting on GSK-3β to promote nuclear accumulation of β-catenin. This was further validated by gain and loss of function studies using cells transfected with either the wild type or mutant GSK-3β constructs. Together these data underpin the role of GSK-3β/β-catenin as a novel target that regulates NPC proliferation mediated by PDGF-BB with implications for therapeutic intervention for reversal of impaired neurogenesis inflicted by Tat.

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Section: Discussionmentioning

confidence: 99%

Platelet-Derived Growth Factor-BB Restores HIV Tat -Mediated Impairment of Neurogenesis: Role of GSK-3β/β-Catenin

Chao

Lü

Yao

et al. 2013

J Neuroimmune Pharmacol

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“…Based on these data, it is difficult to determine how increased dopamine might alter macrophage TNF-α production, and how this would affect the development of HAND. A decrease in this cytokine could reduce neuronal death (McCoy et al 2006) but also decrease the anti-viral activity of TNF-α (Lane et al 1999; Bailer et al 2000), while an increase could promote more inflammation and neurotoxicity (Belarbi et al 2012; Buscemi et al 2007). …”

Section: Dopamine and Hiv In Monocytes And Macrophagesmentioning

confidence: 99%

Drug Induced Increases in CNS Dopamine Alter Monocyte, Macrophage and T Cell Functions: Implications for HAND

Gaskill

Calderon

Coley

et al. 2013

J Neuroimmune Pharmacol

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Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers.

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“…The role of macrophages is at the center of these theories, both as the major substrate for HIV-1 replication and as the source of important toxins [33,34]. A plethora of putative signals and toxins have been implicated, and brain injury and clinical dysfunction are likely to involve several related or overlapping pathways [35][36][37][38].…”

Section: Effect Of Art On Adcmentioning

confidence: 99%

Antiretroviral Therapy and Central Nervous System HIV Type 1 Infection

2008

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Central nervous system (CNS) human immunodeficiency virus type 1 (HIV-1) infection begins during primary viremia and continues throughout the course of untreated systemic infection. Although frequently accompanied by local inflammatory reactions detectable in cerebrospinal fluid (CSF), CNS HIV-1 infection usually is not clinically apparent. In a minority of patients, CNS HIV-1 infection evolves into encephalitis during the late stages of systemic infection, which compromises brain function and presents clinically as acquired immunodeficiency syndrome dementia complex (ADC). Combination antiretroviral therapy (ART) has had a major impact on all aspects of CNS HIV-1 infection and disease. In those with asymptomatic infection, ART usually effectively suppresses HIV-1 in CSF and markedly reduces the incidence of symptomatic ADC. In those presenting with ADC, ART characteristically prevents neurological progression and leads to variable, and at times substantial, recovery. Similarly, treatment has reduced CNS opportunistic infections. With better control of these severe disorders, attention has turned to the possible consequences of chronic silent infection and the issue of whether indolent, low-grade brain injury might require earlier treatment intervention.

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Human immunodeficiency virus type-1 protein Tat induces tumor necrosis factor-α-mediated neurotoxicity

Cited by 65 publications

References 77 publications

Platelet-Derived Growth Factor-BB Restores HIV Tat -Mediated Impairment of Neurogenesis: Role of GSK-3β/β-Catenin

Platelet-Derived Growth Factor-BB Restores HIV Tat -Mediated Impairment of Neurogenesis: Role of GSK-3β/β-Catenin

Drug Induced Increases in CNS Dopamine Alter Monocyte, Macrophage and T Cell Functions: Implications for HAND

Antiretroviral Therapy and Central Nervous System HIV Type 1 Infection

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