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Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1

The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of...

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Autores principales: Völkner, Christin, Liedtke, Maik, Hermann, Andreas, Frech, Moritz J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828283/
https://www.ncbi.nlm.nih.gov/pubmed/33445799
http://dx.doi.org/10.3390/ijms22020710
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author Völkner, Christin
Liedtke, Maik
Hermann, Andreas
Frech, Moritz J.
author_facet Völkner, Christin
Liedtke, Maik
Hermann, Andreas
Frech, Moritz J.
author_sort Völkner, Christin
collection PubMed
description The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency. Clinical manifestations include neurological symptoms and systemic symptoms, such as hepatosplenomegaly and pulmonary manifestations, the latter being particularly pronounced in NPC2 patients. NPC1 and NPC2 are rare diseases with the described neurovisceral clinical picture, but studies with human primary patient-derived neurons and hepatocytes are hardly feasible. Obviously, induced pluripotent stem cells (iPSCs) and their derivatives are an excellent alternative for indispensable studies with these affected cell types to study the multisystemic disease NPC1. Here, we present a review focusing on studies that have used iPSCs for disease modeling and drug discovery in NPC1 and draw a comparison to commonly used NPC1 models.
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spelling pubmed-78282832021-01-25 Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1 Völkner, Christin Liedtke, Maik Hermann, Andreas Frech, Moritz J. Int J Mol Sci Review The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency. Clinical manifestations include neurological symptoms and systemic symptoms, such as hepatosplenomegaly and pulmonary manifestations, the latter being particularly pronounced in NPC2 patients. NPC1 and NPC2 are rare diseases with the described neurovisceral clinical picture, but studies with human primary patient-derived neurons and hepatocytes are hardly feasible. Obviously, induced pluripotent stem cells (iPSCs) and their derivatives are an excellent alternative for indispensable studies with these affected cell types to study the multisystemic disease NPC1. Here, we present a review focusing on studies that have used iPSCs for disease modeling and drug discovery in NPC1 and draw a comparison to commonly used NPC1 models. MDPI 2021-01-12 /pmc/articles/PMC7828283/ /pubmed/33445799 http://dx.doi.org/10.3390/ijms22020710 Text en © 2021 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 Review
Völkner, Christin
Liedtke, Maik
Hermann, Andreas
Frech, Moritz J.
Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1
title Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1
title_full Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1
title_fullStr Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1
title_full_unstemmed Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1
title_short Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1
title_sort pluripotent stem cells for disease modeling and drug discovery in niemann-pick type c1
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828283/
https://www.ncbi.nlm.nih.gov/pubmed/33445799
http://dx.doi.org/10.3390/ijms22020710
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