Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Fella, Eleni, Sokratous, Kleitos, Papacharalambous, Revekka, Kyriacou, Kyriacos, Phillips, Joy, Sanderson, Sam, Panayiotou, Elena, Kyriakides, Theodoros
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
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
_version_ 1783235039318769664
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
work_keys_str_mv AT fellaeleni pharmacologicalstimulationofphagocytosisenhancesamyloidplaqueclearanceevidencefromatransgenicmousemodelofattrneuropathy
AT sokratouskleitos pharmacologicalstimulationofphagocytosisenhancesamyloidplaqueclearanceevidencefromatransgenicmousemodelofattrneuropathy
AT papacharalambousrevekka pharmacologicalstimulationofphagocytosisenhancesamyloidplaqueclearanceevidencefromatransgenicmousemodelofattrneuropathy
AT kyriacoukyriacos pharmacologicalstimulationofphagocytosisenhancesamyloidplaqueclearanceevidencefromatransgenicmousemodelofattrneuropathy
AT phillipsjoy pharmacologicalstimulationofphagocytosisenhancesamyloidplaqueclearanceevidencefromatransgenicmousemodelofattrneuropathy
AT sandersonsam pharmacologicalstimulationofphagocytosisenhancesamyloidplaqueclearanceevidencefromatransgenicmousemodelofattrneuropathy
AT panayiotouelena pharmacologicalstimulationofphagocytosisenhancesamyloidplaqueclearanceevidencefromatransgenicmousemodelofattrneuropathy
AT kyriakidestheodoros pharmacologicalstimulationofphagocytosisenhancesamyloidplaqueclearanceevidencefromatransgenicmousemodelofattrneuropathy