In vivo functions of p75NTR: challenges and opportunities for an emerging therapeutic target
The p75 neurotrophin receptor (p75NTR) functions at the molecular nexus of cell death, survival, and differentiation. In addition to its contribution to neurodegenerative diseases and nervous system injuries, recent studies have revealed unanticipated roles of p75NTR in liver repair, fibrinolysis, l...
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| Published in | Trends in pharmacological sciences (Regular ed.) Vol. 42; no. 9; pp. 772 - 788 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Elsevier Ltd
01.09.2021
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| Subjects | |
| Online Access | Get full text |
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| Abstract | The p75 neurotrophin receptor (p75NTR) functions at the molecular nexus of cell death, survival, and differentiation. In addition to its contribution to neurodegenerative diseases and nervous system injuries, recent studies have revealed unanticipated roles of p75NTR in liver repair, fibrinolysis, lung fibrosis, muscle regeneration, and metabolism. Linking these various p75NTR functions more precisely to specific mechanisms marks p75NTR as an emerging candidate for therapeutic intervention in a wide range of disorders. Indeed, small molecule inhibitors of p75NTR binding to neurotrophins have shown efficacy in models of Alzheimer’s disease (AD) and neurodegeneration. Here, we outline recent advances in understanding p75NTR pleiotropic functions in vivo, and propose an integrated view of p75NTR and its challenges and opportunities as a pharmacological target.
p75NTR is a driver of disease pathogenesis in neurological, metabolic, and fibrotic diseases.p75NTR is highly pleiotropic interacting with multiple ligands, co-receptors, and signaling molecules.Blockade of p75NTR binding to its ligands or intracellular partners has therapeutic potential.Tissue-specific selective targeting of p75NTR may avoid potentially adverse on-target effects. |
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| AbstractList | The p75 neurotrophin receptor (p75NTR) functions at the molecular nexus of cell death, survival, and differentiation. In addition to its contribution to neurodegenerative diseases and nervous system injuries, recent studies have revealed unanticipated roles of p75NTR in liver repair, fibrinolysis, lung fibrosis, muscle regeneration, and metabolism. Linking these various p75NTR functions more precisely to specific mechanisms marks p75NTR as an emerging candidate for therapeutic intervention in a wide range of disorders. Indeed, small molecule inhibitors of p75NTR binding to neurotrophins have shown efficacy in models of Alzheimer’s disease (AD) and neurodegeneration. Here, we outline recent advances in understanding p75NTR pleiotropic functions in vivo, and propose an integrated view of p75NTR and its challenges and opportunities as a pharmacological target.
p75NTR is a driver of disease pathogenesis in neurological, metabolic, and fibrotic diseases.p75NTR is highly pleiotropic interacting with multiple ligands, co-receptors, and signaling molecules.Blockade of p75NTR binding to its ligands or intracellular partners has therapeutic potential.Tissue-specific selective targeting of p75NTR may avoid potentially adverse on-target effects. The p75 neurotrophin receptor (p75 NTR ) functions at the molecular nexus of cell death, survival, and differentiation. In addition to its contribution to neurodegenerative diseases and nervous system injuries, recent studies have revealed unanticipated roles of p75 NTR in liver repair, fibrinolysis, lung fibrosis, muscle regeneration and metabolism. Linking these various p75 NTR functions more precisely to specific mechanisms marks p75 NTR as an emerging candidate for therapeutic intervention in a wide range of disorders. Indeed, small molecule inhibitors of p75 NTR binding to neurotrophins have shown efficacy in models of Alzheimer’s disease and neurodegeneration. Here, we outline recent advances in understanding p75 NTR pleiotropic functions in vivo , and propose an integrated view of p75 NTR and its challenges and opportunities as a pharmacological target. |
| Author | Baeza-Raja, Bernat Le Moan, Natacha Schachtrup, Christian Malik, Subash C. Sozmen, Elif G. Akassoglou, Katerina |
| AuthorAffiliation | 1 Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany 3 Gladstone Institutes, San Francisco, CA, USA 2 Center for Neurovascular Brain Immunology at Gladstone and UCSF; Gladstone Institutes, San Francisco, CA, USA; Department of Neurology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA 4 Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Basics in NeuroModulation (NeuroModul Basics), Faculty of Medicine, University of Freiburg, Freiburg, Germany |
| AuthorAffiliation_xml | – name: 3 Gladstone Institutes, San Francisco, CA, USA – name: 2 Center for Neurovascular Brain Immunology at Gladstone and UCSF; Gladstone Institutes, San Francisco, CA, USA; Department of Neurology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA – name: 4 Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Basics in NeuroModulation (NeuroModul Basics), Faculty of Medicine, University of Freiburg, Freiburg, Germany – name: 1 Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany |
| Author_xml | – sequence: 1 givenname: Subash C. surname: Malik fullname: Malik, Subash C. organization: Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany – sequence: 2 givenname: Elif G. surname: Sozmen fullname: Sozmen, Elif G. organization: Center for Neurovascular Brain Immunology at Gladstone and UCSF – sequence: 3 givenname: Bernat surname: Baeza-Raja fullname: Baeza-Raja, Bernat organization: Gladstone Institutes, San Francisco, CA, USA – sequence: 4 givenname: Natacha surname: Le Moan fullname: Le Moan, Natacha organization: Gladstone Institutes, San Francisco, CA, USA – sequence: 5 givenname: Katerina surname: Akassoglou fullname: Akassoglou, Katerina organization: Center for Neurovascular Brain Immunology at Gladstone and UCSF – sequence: 6 givenname: Christian surname: Schachtrup fullname: Schachtrup, Christian email: christian.schachtrup@anat.uni-freiburg.de organization: Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany |
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| Title | In vivo functions of p75NTR: challenges and opportunities for an emerging therapeutic target |
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