The Experts below are selected from a list of 51 Experts worldwide ranked by ideXlab platform

Claes Wahlestedt - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation
    Nature Biotechnology, 2012
    Co-Authors: Farzaneh Modarresi, Mohammad Ali Faghihi, Miguel A. Lopez-toledano, Roya Pedram Fatemi, Marco Magistri, Marcel P. Van Der Brug, Shaun P Brothers, Claes Wahlestedt
    Abstract:

    Methods for specific gene silencing have advanced as far as clinical trials, but a similar set of tools does not exist for increasing gene expression. Modarresi et al . demonstrate gene-specific upregulation in vivo by treating mice with oligonucleotides that inhibit the function of natural antisense transcripts. The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF -AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo . We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and Ephrin Receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.

  • Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation
    Nature biotechnology, 2012
    Co-Authors: Farzaneh Modarresi, Mohammad Ali Faghihi, Miguel A. Lopez-toledano, Roya Pedram Fatemi, Marco Magistri, Marcel P. Van Der Brug, Claes Wahlestedt
    Abstract:

    The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF-AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo. We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and Ephrin Receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.

Farzaneh Modarresi - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation
    Nature Biotechnology, 2012
    Co-Authors: Farzaneh Modarresi, Mohammad Ali Faghihi, Miguel A. Lopez-toledano, Roya Pedram Fatemi, Marco Magistri, Marcel P. Van Der Brug, Shaun P Brothers, Claes Wahlestedt
    Abstract:

    Methods for specific gene silencing have advanced as far as clinical trials, but a similar set of tools does not exist for increasing gene expression. Modarresi et al . demonstrate gene-specific upregulation in vivo by treating mice with oligonucleotides that inhibit the function of natural antisense transcripts. The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF -AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo . We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and Ephrin Receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.

  • Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation
    Nature biotechnology, 2012
    Co-Authors: Farzaneh Modarresi, Mohammad Ali Faghihi, Miguel A. Lopez-toledano, Roya Pedram Fatemi, Marco Magistri, Marcel P. Van Der Brug, Claes Wahlestedt
    Abstract:

    The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF-AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo. We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and Ephrin Receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.

Kamel Khalili - One of the best experts on this subject based on the ideXlab platform.

  • tnf α tnfr2 regulatory axis stimulates ephB2 mediated neuroregeneration via activation of nf κb
    Journal of Cellular Physiology, 2016
    Co-Authors: Paul D Pozniak, Armine Darbinyan, Kamel Khalili
    Abstract:

    HIV-1 infected individuals are at high risk of developing HIV-associated neurocognitive disorders (HAND) as HIV infection leads to neuronal injury and synaptic loss in the central nervous system (CNS). The neurotoxic effects of HIV-1 are primarily a result of viral replication leading to the production of inflammatory chemokines and cytokines, including TNF-α. Given an important role of TNF-α in regulating synaptic plasticity, we investigated the effects of TNF-α on the development of neuronal processes after mechanical injury, and we showed that TNF-α treatment stimulates the regrowth of neuronal processes. To investigate transcriptional effects of TNF-α on synaptic plasticity, we analyzed both human neurosphere and isolated neuronal cultures for the regulation of genes central to synaptic alterations during learning and memory. TNF-α treatment upregulated Ephrin Receptor B2 (EphB2), which is strongly involved in dendritic arborization and synaptic integrity. TNF-α strongly activates the NF-κB pathway, therefore, we propose that TNF-α-induced neurite regrowth occurs primarily through EphB2 signaling via stimulation of NF-κB. EphB2 promoter activity increased with TNF-α treatment and overexpression of NF-κB. Direct binding of NF-κB to the EphB2 promoter occurred in the ChIP assay, and site-directed mutagenesis identified binding sites involved in TNF-α-induced EphB2 activation. TNF-α induction of EphB2 was determined to occur specifically through TNF-α Receptor 2 (TNFR2) activation in human primary fetal neurons. Our observations provide a new avenue for the investigation on the impact of TNF-α in the context of HIV-1 neuronal cell damage as well as providing a potential therapeutic target in TNFR2 activation of EphB2.

  • TNF-α/TNFR2 Regulatory Axis Stimulates EphB2-Mediated Neuroregeneration Via Activation of NF-κB.
    Journal of cellular physiology, 2015
    Co-Authors: Paul D Pozniak, Armine Darbinyan, Kamel Khalili
    Abstract:

    HIV-1 infected individuals are at high risk of developing HIV-associated neurocognitive disorders (HAND) as HIV infection leads to neuronal injury and synaptic loss in the central nervous system (CNS). The neurotoxic effects of HIV-1 are primarily a result of viral replication leading to the production of inflammatory chemokines and cytokines, including TNF-α. Given an important role of TNF-α in regulating synaptic plasticity, we investigated the effects of TNF-α on the development of neuronal processes after mechanical injury, and we showed that TNF-α treatment stimulates the regrowth of neuronal processes. To investigate transcriptional effects of TNF-α on synaptic plasticity, we analyzed both human neurosphere and isolated neuronal cultures for the regulation of genes central to synaptic alterations during learning and memory. TNF-α treatment upregulated Ephrin Receptor B2 (EphB2), which is strongly involved in dendritic arborization and synaptic integrity. TNF-α strongly activates the NF-κB pathway, therefore, we propose that TNF-α-induced neurite regrowth occurs primarily through EphB2 signaling via stimulation of NF-κB. EphB2 promoter activity increased with TNF-α treatment and overexpression of NF-κB. Direct binding of NF-κB to the EphB2 promoter occurred in the ChIP assay, and site-directed mutagenesis identified binding sites involved in TNF-α-induced EphB2 activation. TNF-α induction of EphB2 was determined to occur specifically through TNF-α Receptor 2 (TNFR2) activation in human primary fetal neurons. Our observations provide a new avenue for the investigation on the impact of TNF-α in the context of HIV-1 neuronal cell damage as well as providing a potential therapeutic target in TNFR2 activation of EphB2.

Marcel P. Van Der Brug - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation
    Nature Biotechnology, 2012
    Co-Authors: Farzaneh Modarresi, Mohammad Ali Faghihi, Miguel A. Lopez-toledano, Roya Pedram Fatemi, Marco Magistri, Marcel P. Van Der Brug, Shaun P Brothers, Claes Wahlestedt
    Abstract:

    Methods for specific gene silencing have advanced as far as clinical trials, but a similar set of tools does not exist for increasing gene expression. Modarresi et al . demonstrate gene-specific upregulation in vivo by treating mice with oligonucleotides that inhibit the function of natural antisense transcripts. The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF -AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo . We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and Ephrin Receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.

  • Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation
    Nature biotechnology, 2012
    Co-Authors: Farzaneh Modarresi, Mohammad Ali Faghihi, Miguel A. Lopez-toledano, Roya Pedram Fatemi, Marco Magistri, Marcel P. Van Der Brug, Claes Wahlestedt
    Abstract:

    The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF-AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo. We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and Ephrin Receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.

Mohammad Ali Faghihi - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation
    Nature Biotechnology, 2012
    Co-Authors: Farzaneh Modarresi, Mohammad Ali Faghihi, Miguel A. Lopez-toledano, Roya Pedram Fatemi, Marco Magistri, Marcel P. Van Der Brug, Shaun P Brothers, Claes Wahlestedt
    Abstract:

    Methods for specific gene silencing have advanced as far as clinical trials, but a similar set of tools does not exist for increasing gene expression. Modarresi et al . demonstrate gene-specific upregulation in vivo by treating mice with oligonucleotides that inhibit the function of natural antisense transcripts. The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF -AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo . We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and Ephrin Receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.

  • Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation
    Nature biotechnology, 2012
    Co-Authors: Farzaneh Modarresi, Mohammad Ali Faghihi, Miguel A. Lopez-toledano, Roya Pedram Fatemi, Marco Magistri, Marcel P. Van Der Brug, Claes Wahlestedt
    Abstract:

    The ability to specifically upregulate genes in vivo holds great therapeutic promise. Here we show that inhibition or degradation of natural antisense transcripts (NATs) by single-stranded oligonucleotides or siRNAs can transiently and reversibly upregulate locus-specific gene expression. Brain-derived neurotrophic factor (BDNF) is normally repressed by a conserved noncoding antisense RNA transcript, BDNF-AS. Inhibition of this transcript upregulates BDNF mRNA by two- to sevenfold, alters chromatin marks at the BDNF locus, leads to increased protein levels and induces neuronal outgrowth and differentiation both in vitro and in vivo. We also show that inhibition of NATs leads to increases in glial-derived neurotrophic factor (GDNF) and Ephrin Receptor B2 (EPHB2) mRNA. Our data suggest that pharmacological approaches targeting NATs can confer locus-specific gene upregulation effects.