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The p75 neurotrophin receptor: at the crossroad of neural repair and death

The strong repair and pro-survival functions of neurotrophins at their primary receptors, TrkA, TrkB and TrkC, have made them attractive candidates for treatment of nervous system injury and disease. However, difficulties with the clinical implementation of neurotrophin therapies have prompted the s...

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Autores principales: Meeker, Rick B., Williams, Kimberly S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468762/
https://www.ncbi.nlm.nih.gov/pubmed/26109945
http://dx.doi.org/10.4103/1673-5374.156967
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author Meeker, Rick B.
Williams, Kimberly S.
author_facet Meeker, Rick B.
Williams, Kimberly S.
author_sort Meeker, Rick B.
collection PubMed
description The strong repair and pro-survival functions of neurotrophins at their primary receptors, TrkA, TrkB and TrkC, have made them attractive candidates for treatment of nervous system injury and disease. However, difficulties with the clinical implementation of neurotrophin therapies have prompted the search for treatments that are stable, easier to deliver and allow more precise regulation of neurotrophin actions. Recently, the p75 neurotrophin receptor (p75(NTR)) has emerged as a potential target for pharmacological control of neurotrophin activity, supported in part by studies demonstrating 1) regulation of neural plasticity in the mature nervous system, 2) promotion of adult neurogenesis and 3) increased expression in neurons, macrophages, microglia, astrocytes and/or Schwann cells in response to injury and neurodegenerative diseases. Although the receptor has no intrinsic catalytic activity it interacts with and modulates the function of TrkA, TrkB, and TrkC, as well as sortilin and the Nogo receptor. This provides substantial cellular and molecular diversity for regulation of neuron survival, neurogenesis, immune responses and processes that support neural function. Upregulation of the p75(NTR) under pathological conditions places the receptor in a key position to control numerous processes necessary for nervous system recovery. Support for this possibility has come from recent studies showing that small, non-peptide p75(NTR) ligands can selectively modify pro-survival and repair functions. While a great deal remains to be discovered about the wide ranging functions of the p75(NTR), studies summarized in this review highlight the immense potential for development of novel neuroprotective and neurorestorative therapies.
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spelling pubmed-44687622015-06-24 The p75 neurotrophin receptor: at the crossroad of neural repair and death Meeker, Rick B. Williams, Kimberly S. Neural Regen Res Invited Review The strong repair and pro-survival functions of neurotrophins at their primary receptors, TrkA, TrkB and TrkC, have made them attractive candidates for treatment of nervous system injury and disease. However, difficulties with the clinical implementation of neurotrophin therapies have prompted the search for treatments that are stable, easier to deliver and allow more precise regulation of neurotrophin actions. Recently, the p75 neurotrophin receptor (p75(NTR)) has emerged as a potential target for pharmacological control of neurotrophin activity, supported in part by studies demonstrating 1) regulation of neural plasticity in the mature nervous system, 2) promotion of adult neurogenesis and 3) increased expression in neurons, macrophages, microglia, astrocytes and/or Schwann cells in response to injury and neurodegenerative diseases. Although the receptor has no intrinsic catalytic activity it interacts with and modulates the function of TrkA, TrkB, and TrkC, as well as sortilin and the Nogo receptor. This provides substantial cellular and molecular diversity for regulation of neuron survival, neurogenesis, immune responses and processes that support neural function. Upregulation of the p75(NTR) under pathological conditions places the receptor in a key position to control numerous processes necessary for nervous system recovery. Support for this possibility has come from recent studies showing that small, non-peptide p75(NTR) ligands can selectively modify pro-survival and repair functions. While a great deal remains to be discovered about the wide ranging functions of the p75(NTR), studies summarized in this review highlight the immense potential for development of novel neuroprotective and neurorestorative therapies. Medknow Publications & Media Pvt Ltd 2015-05 /pmc/articles/PMC4468762/ /pubmed/26109945 http://dx.doi.org/10.4103/1673-5374.156967 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Invited Review
Meeker, Rick B.
Williams, Kimberly S.
The p75 neurotrophin receptor: at the crossroad of neural repair and death
title The p75 neurotrophin receptor: at the crossroad of neural repair and death
title_full The p75 neurotrophin receptor: at the crossroad of neural repair and death
title_fullStr The p75 neurotrophin receptor: at the crossroad of neural repair and death
title_full_unstemmed The p75 neurotrophin receptor: at the crossroad of neural repair and death
title_short The p75 neurotrophin receptor: at the crossroad of neural repair and death
title_sort p75 neurotrophin receptor: at the crossroad of neural repair and death
topic Invited Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468762/
https://www.ncbi.nlm.nih.gov/pubmed/26109945
http://dx.doi.org/10.4103/1673-5374.156967
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