Regulation of neural cell survival by HIV-1 infection

Jones, Gareth; Power, Christopher

doi:10.1016/j.nbd.2005.07.018

Cited by 79 publications

(78 citation statements)

References 249 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As neurons are not the primary targets of HIV in the brain -the virus mostly infects macrophages and microglia and, to a lesser extent, astroglia -the neuropathogenesis of AIDS is not completely understood. A number of viral and cellular factors produced by infected or activated cells over a long period of time appear to be responsible for the neuronal damage caused by HIV (recent reviews: Gartner and Liu, 2002;Gonzalez-Scarano and MartinGarcia, 2005;Jones and Power, 2006;Mattson et al, 2005). One of these factors is the HIV envelope protein gp120 that binds to chemokine receptors (i.e., CCR5 and CXCR4) on the surface of target cells, including neurons (Gartner and Liu, 2002;GonzalezScarano and Martin-Garcia, 2005;Hesselgesser et al, 1998;Jones and Power, 2006;Mattson et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…A number of viral and cellular factors produced by infected or activated cells over a long period of time appear to be responsible for the neuronal damage caused by HIV (recent reviews: Gartner and Liu, 2002;Gonzalez-Scarano and MartinGarcia, 2005;Jones and Power, 2006;Mattson et al, 2005). One of these factors is the HIV envelope protein gp120 that binds to chemokine receptors (i.e., CCR5 and CXCR4) on the surface of target cells, including neurons (Gartner and Liu, 2002;GonzalezScarano and Martin-Garcia, 2005;Hesselgesser et al, 1998;Jones and Power, 2006;Mattson et al, 2005). Several in vitro and in vivo studies have shown the neurotoxic potential of the envelope protein and the involvement of chemokine receptors in this process (Gartner and Liu, 2002;Gonzalez-Scarano and Martin-Garcia, 2005;Jones and Power, 2006;Mattson et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…One of these factors is the HIV envelope protein gp120 that binds to chemokine receptors (i.e., CCR5 and CXCR4) on the surface of target cells, including neurons (Gartner and Liu, 2002;GonzalezScarano and Martin-Garcia, 2005;Hesselgesser et al, 1998;Jones and Power, 2006;Mattson et al, 2005). Several in vitro and in vivo studies have shown the neurotoxic potential of the envelope protein and the involvement of chemokine receptors in this process (Gartner and Liu, 2002;Gonzalez-Scarano and Martin-Garcia, 2005;Jones and Power, 2006;Mattson et al, 2005). The interaction of the co-receptors with the viral protein only partially resembles the interaction with their natural ligands , suggesting that activation of chemokine receptors may lead to cell death.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology

Shimizu

Khan

Hippensteel

et al. 2007

Neurobiology of Disease

View full text Add to dashboard Cite

This study sought to determine the role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology. We studied the effect of the HIV envelope protein gp120 on the expression of E2F1-dependent apoptotic proteins in human and rodent neurons and examined the expression pattern of E2F1 in the brain of HIVinfected individuals. Our findings suggest that in cultured neurons gp120 increased E2F1 levels in the nucleus, stimulated its transcriptional activity and enhanced the expression of the E2F1 target proteins Cdc2 and Puma. Studies with neuronal cultures from E2F1 deficient mice demonstrated that the transcription factor is required for gp120-induced neurotoxicity and up-regulation of Cdc2 and Puma. Levels of E2F1 protein were greater in the nucleus of neurons in brains of HIVinfected patients exhibiting dementia when compared to HIV-negative subjects or HIV-positive neurologically normal patients. Overall, these studies indicate that E2F1 is primarily involved in CXCR4-mediated neurotoxicity and HIV neuropathogenesis.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology

Shimizu

Khan

Hippensteel

et al. 2007

Neurobiology of Disease

View full text Add to dashboard Cite

show abstract

“…13,14 In any case, HIV-1/gp120 mediates infection or activation of macrophages and microglia. [1][2][3]7,15 This leads to toxin production by these monocytic cells, which seems essential for a pronounced neurodegenerative effect.…”

mentioning

confidence: 99%

“…20 Additionally, astrocytes and neurons possess CCR5 and CXCR4, consistent with the observation that under certain conditions chemokine receptors on these cells can also influence HIV-induced neuronal damage. 7,13,[21][22][23][24][25] Nevertheless, the exact pathologic function of CXCR4 and CCR5 in brain cells remains to be defined. Interestingly, brains from humans with HAD and transgenic mice expressing gp120 share many neuropathological features, including synaptic and dendritic damage, frank loss of neurons and activation of glia.…”

mentioning

confidence: 99%

HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection

et al. 2006

View full text Add to dashboard Cite

The chemokine receptors CCR5 and CXCR4 serve, in addition to CD4, as coreceptors for human immunodeficiency virus-1 (HIV-1), and infection with HIV-1 can cause dementia. In brain-derived cells, HIV-1 envelope glycoprotein gp120 initiates a signaling cascade that involves p38 mitogen-activated protein kinase and leads to neuronal cell death. Using mixed neuronal/glial cultures from rats and mice genetically deficient in one or both HIV coreceptors, we show here that CCR5, CXCR4 or both can mediate HIV/ gp120 neurotoxicity depending on the viral strain. Paradoxically, we also found evidence for a CCR5-mediated neuroprotective pathway. We identify protein kinase Akt/PKB as an essential component of this pathway, which can be triggered by the CCR5 agonists macrophage inflammatory protein-1b and regulated-and-normal-T-cell-expressed-and-secreted. Moreover, these CCR5 ligands prevent neuronal cell death induced by stromal cell-derived factor-1, a CXCR4 agonist. Both neurons and glia coexpress CXCR4 and CCR5. Ca 2 þ imaging experiments demonstrate that engagement of CCR5 prevents CXCR4-triggered increases in intracellular free Ca 2 þ . This finding suggests that CCR5 ligands can protect neurons at least, in part, by modulating CXCR4-mediated toxicity through heterologous desensitization.

show abstract

Lipid Nanoparticle Delivery of Chemically Modified NGF^R100W mRNA Alleviates Peripheral Neuropathy

Yang

Xia

et al. 2022

Adv Healthcare Materials

View full text Add to dashboard Cite

Messenger RNA (mRNA) carries genetic instructions to the cell machinery for the transient production of antigens or therapeutic proteins and shows enormous potential in vaccine development, cancer immunotherapy, protein replacement therapy, and genome engineering. Here, the synthesis of chemically modified nerve growth factor mutant (NGF R100W ) mRNA through in vitro transcription is described. After the replacement of the original signal peptide sequence with the Ig Kappa leader sequence, codon-optimized NGF R100W mRNA yielded high secretion of mature NGF R100W , which promotes axon growth in PC12 cells. Using lipid nanoparticle (LNP)-delivery of N1-methylpseudouridine-modified mRNA in mice, NGF R100W -mRNA-LNPs result in the successful expression of NGF R100W protein, which significantly reduces nociceptive activity compared to that of NGF WT . This indicates that NGF R100W derived from exogenous mRNA elicited "painless" neuroprotective activity. Additionally, the therapeutic value of NGF R100W mRNA is established in a paclitaxel-induced peripheral neuropathy model by demonstrating the rapid recovery of intraepidermal nerve fibers. The results show that in vitro-transcribed mRNA has significant flexibility in sequence design and fast in vivo functional validation of target proteins. Furthermore, the results highlight the therapeutic potential of mRNA as a supplement to beneficial proteins for preventing or reversing some chronic medical conditions, such as peripheral neuropathy.

show abstract

Regulation of neural cell survival by HIV-1 infection

Cited by 79 publications

References 249 publications

Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology

Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology

HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection

Lipid Nanoparticle Delivery of Chemically Modified NGF^R100W mRNA Alleviates Peripheral Neuropathy

Contact Info

Product

Resources

About

Regulation of neural cell survival by HIV-1 infection

Cited by 79 publications

References 249 publications

Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology

Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology

HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection

Lipid Nanoparticle Delivery of Chemically Modified NGFR100W mRNA Alleviates Peripheral Neuropathy

Contact Info

Product

Resources

About

Lipid Nanoparticle Delivery of Chemically Modified NGF^R100W mRNA Alleviates Peripheral Neuropathy