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Pharmacological Stimulation of Phagocytosis Enhances Amyloid Plaque Clearance; Evidence from a Transgenic Mouse Model of ATTR Neuropathy
Hereditary ATTR V30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by deposition of aberrant transthyretin (TTR). Immunohistochemical examination of sural nerve biopsies in patients with amyloidotic neuropathy show co-aggregation of TTR with several proteins...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423984/ https://www.ncbi.nlm.nih.gov/pubmed/28539873 http://dx.doi.org/10.3389/fnmol.2017.00138 |
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author | Fella, Eleni Sokratous, Kleitos Papacharalambous, Revekka Kyriacou, Kyriacos Phillips, Joy Sanderson, Sam Panayiotou, Elena Kyriakides, Theodoros |
author_facet | Fella, Eleni Sokratous, Kleitos Papacharalambous, Revekka Kyriacou, Kyriacos Phillips, Joy Sanderson, Sam Panayiotou, Elena Kyriakides, Theodoros |
author_sort | Fella, Eleni |
collection | PubMed |
description | Hereditary ATTR V30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by deposition of aberrant transthyretin (TTR). Immunohistochemical examination of sural nerve biopsies in patients with amyloidotic neuropathy show co-aggregation of TTR with several proteins; including apolipoprotein E, serum amyloid P and components of the complement cascade. Complement activation and macrophages are increasingly recognized to play a crucial role in amyloidogenesis at the tissue bed level. In the current study we test the effect of two C5a receptor agonists and a C5a receptor antagonist (PMX53) on disease phenotype in ATTR V30M mice. Our results indicate that amyloid deposition was significantly reduced following treatment with the C5a receptor agonists, while treatment with the antagonist resulted in a significant increase of amyloid load. Administration of the C5a receptor agonists triggered increased recruitment of phagocytic cells resulting in clearance of amyloid deposits. |
format | Online Article Text |
id | pubmed-5423984 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54239842017-05-24 Pharmacological Stimulation of Phagocytosis Enhances Amyloid Plaque Clearance; Evidence from a Transgenic Mouse Model of ATTR Neuropathy Fella, Eleni Sokratous, Kleitos Papacharalambous, Revekka Kyriacou, Kyriacos Phillips, Joy Sanderson, Sam Panayiotou, Elena Kyriakides, Theodoros Front Mol Neurosci Neuroscience Hereditary ATTR V30M amyloidosis is a lethal autosomal dominant sensorimotor and autonomic neuropathy caused by deposition of aberrant transthyretin (TTR). Immunohistochemical examination of sural nerve biopsies in patients with amyloidotic neuropathy show co-aggregation of TTR with several proteins; including apolipoprotein E, serum amyloid P and components of the complement cascade. Complement activation and macrophages are increasingly recognized to play a crucial role in amyloidogenesis at the tissue bed level. In the current study we test the effect of two C5a receptor agonists and a C5a receptor antagonist (PMX53) on disease phenotype in ATTR V30M mice. Our results indicate that amyloid deposition was significantly reduced following treatment with the C5a receptor agonists, while treatment with the antagonist resulted in a significant increase of amyloid load. Administration of the C5a receptor agonists triggered increased recruitment of phagocytic cells resulting in clearance of amyloid deposits. Frontiers Media S.A. 2017-05-10 /pmc/articles/PMC5423984/ /pubmed/28539873 http://dx.doi.org/10.3389/fnmol.2017.00138 Text en Copyright © 2017 Fella, Sokratous, Papacharalambous, Kyriakou, Phillips, Sanderson, Panayiotou and Kyriakides. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Fella, Eleni Sokratous, Kleitos Papacharalambous, Revekka Kyriacou, Kyriacos Phillips, Joy Sanderson, Sam Panayiotou, Elena Kyriakides, Theodoros Pharmacological Stimulation of Phagocytosis Enhances Amyloid Plaque Clearance; Evidence from a Transgenic Mouse Model of ATTR Neuropathy |
title | Pharmacological Stimulation of Phagocytosis Enhances Amyloid Plaque Clearance; Evidence from a Transgenic Mouse Model of ATTR Neuropathy |
title_full | Pharmacological Stimulation of Phagocytosis Enhances Amyloid Plaque Clearance; Evidence from a Transgenic Mouse Model of ATTR Neuropathy |
title_fullStr | Pharmacological Stimulation of Phagocytosis Enhances Amyloid Plaque Clearance; Evidence from a Transgenic Mouse Model of ATTR Neuropathy |
title_full_unstemmed | Pharmacological Stimulation of Phagocytosis Enhances Amyloid Plaque Clearance; Evidence from a Transgenic Mouse Model of ATTR Neuropathy |
title_short | Pharmacological Stimulation of Phagocytosis Enhances Amyloid Plaque Clearance; Evidence from a Transgenic Mouse Model of ATTR Neuropathy |
title_sort | pharmacological stimulation of phagocytosis enhances amyloid plaque clearance; evidence from a transgenic mouse model of attr neuropathy |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423984/ https://www.ncbi.nlm.nih.gov/pubmed/28539873 http://dx.doi.org/10.3389/fnmol.2017.00138 |
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