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Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1
Niemann–Pick disease type C1 (NPC1) is a fatal neurovisceral lysosomal lipid storage disorder. The mutation of the NPC1 protein affects the homeostasis and transport of cholesterol and glycosphingolipids from late endosomes/lysosomes to the endoplasmic reticulum resulting in progressive neurodegener...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412361/ https://www.ncbi.nlm.nih.gov/pubmed/28383485 http://dx.doi.org/10.3390/ijms18040777 |
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author | Meyer, Anja Wree, Andreas Günther, René Holzmann, Carsten Schmitt, Oliver Rolfs, Arndt Witt, Martin |
author_facet | Meyer, Anja Wree, Andreas Günther, René Holzmann, Carsten Schmitt, Oliver Rolfs, Arndt Witt, Martin |
author_sort | Meyer, Anja |
collection | PubMed |
description | Niemann–Pick disease type C1 (NPC1) is a fatal neurovisceral lysosomal lipid storage disorder. The mutation of the NPC1 protein affects the homeostasis and transport of cholesterol and glycosphingolipids from late endosomes/lysosomes to the endoplasmic reticulum resulting in progressive neurodegeneration. Since olfactory impairment is one of the earliest symptoms in many neurodegenerative disorders, we focused on alterations of the olfactory epithelium in an NPC1 mouse model. Previous findings revealed severe morphological and immunohistochemical alterations in the olfactory system of NPC1(−/−) mutant mice compared with healthy controls (NPC1(+/+)). Based on immunohistochemical evaluation of the olfactory epithelium, we analyzed the impact of neurodegeneration in the olfactory epithelium of NPC1(−/−) mice and observed considerable loss of mature olfactory receptor neurons as well as an increased number of proliferating and apoptotic cells. Additionally, after administration of two different therapy approaches using either a combination of miglustat, 2-hydroxypropyl-β-cyclodextrin (HPβCD) and allopregnanolone or a monotherapy with HPβCD, we recorded a remarkable reduction of morphological damages in NPC1(−/−) mice and an up to four-fold increase of proliferating cells within the olfactory epithelium. Numbers of mature olfactory receptor neurons doubled after both therapy approaches. Interestingly, we also observed therapy-induced alterations in treated NPC1(+/+) controls. Thus, olfactory testing may provide useful information to monitor pharmacologic treatment approaches in human NPC1. |
format | Online Article Text |
id | pubmed-5412361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-54123612017-05-05 Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1 Meyer, Anja Wree, Andreas Günther, René Holzmann, Carsten Schmitt, Oliver Rolfs, Arndt Witt, Martin Int J Mol Sci Article Niemann–Pick disease type C1 (NPC1) is a fatal neurovisceral lysosomal lipid storage disorder. The mutation of the NPC1 protein affects the homeostasis and transport of cholesterol and glycosphingolipids from late endosomes/lysosomes to the endoplasmic reticulum resulting in progressive neurodegeneration. Since olfactory impairment is one of the earliest symptoms in many neurodegenerative disorders, we focused on alterations of the olfactory epithelium in an NPC1 mouse model. Previous findings revealed severe morphological and immunohistochemical alterations in the olfactory system of NPC1(−/−) mutant mice compared with healthy controls (NPC1(+/+)). Based on immunohistochemical evaluation of the olfactory epithelium, we analyzed the impact of neurodegeneration in the olfactory epithelium of NPC1(−/−) mice and observed considerable loss of mature olfactory receptor neurons as well as an increased number of proliferating and apoptotic cells. Additionally, after administration of two different therapy approaches using either a combination of miglustat, 2-hydroxypropyl-β-cyclodextrin (HPβCD) and allopregnanolone or a monotherapy with HPβCD, we recorded a remarkable reduction of morphological damages in NPC1(−/−) mice and an up to four-fold increase of proliferating cells within the olfactory epithelium. Numbers of mature olfactory receptor neurons doubled after both therapy approaches. Interestingly, we also observed therapy-induced alterations in treated NPC1(+/+) controls. Thus, olfactory testing may provide useful information to monitor pharmacologic treatment approaches in human NPC1. MDPI 2017-04-06 /pmc/articles/PMC5412361/ /pubmed/28383485 http://dx.doi.org/10.3390/ijms18040777 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Meyer, Anja Wree, Andreas Günther, René Holzmann, Carsten Schmitt, Oliver Rolfs, Arndt Witt, Martin Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1 |
title | Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1 |
title_full | Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1 |
title_fullStr | Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1 |
title_full_unstemmed | Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1 |
title_short | Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1 |
title_sort | increased regenerative capacity of the olfactory epithelium in niemann–pick disease type c1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412361/ https://www.ncbi.nlm.nih.gov/pubmed/28383485 http://dx.doi.org/10.3390/ijms18040777 |
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