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Peripheral immune system modulates Purkinje cell degeneration in Niemann–Pick disease type C1
Niemann–Pick disease type C1 (NPC1) is a fatal lysosomal storage disorder characterized by progressive neuronal degeneration. Its key pathogenic events remain largely unknown. We have, herein, found that neonatal BM–derived cell transplantation can ameliorate Purkinje cell degeneration in NPC1 mice....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300197/ https://www.ncbi.nlm.nih.gov/pubmed/37369603 http://dx.doi.org/10.26508/lsa.202201881 |
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author | Yasuda, Toru Uchiyama, Toru Watanabe, Nobuyuki Ito, Noriko Nakabayashi, Kazuhiko Mochizuki, Hideki Onodera, Masafumi |
author_facet | Yasuda, Toru Uchiyama, Toru Watanabe, Nobuyuki Ito, Noriko Nakabayashi, Kazuhiko Mochizuki, Hideki Onodera, Masafumi |
author_sort | Yasuda, Toru |
collection | PubMed |
description | Niemann–Pick disease type C1 (NPC1) is a fatal lysosomal storage disorder characterized by progressive neuronal degeneration. Its key pathogenic events remain largely unknown. We have, herein, found that neonatal BM–derived cell transplantation can ameliorate Purkinje cell degeneration in NPC1 mice. We subsequently addressed the impact of the peripheral immune system on the neuropathogenesis observed in NPC1 mice. The depletion of mature lymphocytes promoted NPC1 phenotypes, thereby suggesting a neuroprotective effect of lymphocytes. Moreover, the peripheral infusion of CD4-positive cells (specifically, of regulatory T cells) from normal healthy donor ameliorated the cerebellar ataxic phenotype and enhanced the survival of Purkinje cells. Conversely, the depletion of regulatory T cells enhanced the onset of the neurological phenotype. On the other hand, circulating inflammatory monocytes were found to be involved in the progression of Purkinje cell degeneration, whereas the depletion of resident microglia had little effect. Our findings reveal a novel role of the adaptive and the innate immune systems in NPC1 neuropathology. |
format | Online Article Text |
id | pubmed-10300197 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-103001972023-06-29 Peripheral immune system modulates Purkinje cell degeneration in Niemann–Pick disease type C1 Yasuda, Toru Uchiyama, Toru Watanabe, Nobuyuki Ito, Noriko Nakabayashi, Kazuhiko Mochizuki, Hideki Onodera, Masafumi Life Sci Alliance Research Articles Niemann–Pick disease type C1 (NPC1) is a fatal lysosomal storage disorder characterized by progressive neuronal degeneration. Its key pathogenic events remain largely unknown. We have, herein, found that neonatal BM–derived cell transplantation can ameliorate Purkinje cell degeneration in NPC1 mice. We subsequently addressed the impact of the peripheral immune system on the neuropathogenesis observed in NPC1 mice. The depletion of mature lymphocytes promoted NPC1 phenotypes, thereby suggesting a neuroprotective effect of lymphocytes. Moreover, the peripheral infusion of CD4-positive cells (specifically, of regulatory T cells) from normal healthy donor ameliorated the cerebellar ataxic phenotype and enhanced the survival of Purkinje cells. Conversely, the depletion of regulatory T cells enhanced the onset of the neurological phenotype. On the other hand, circulating inflammatory monocytes were found to be involved in the progression of Purkinje cell degeneration, whereas the depletion of resident microglia had little effect. Our findings reveal a novel role of the adaptive and the innate immune systems in NPC1 neuropathology. Life Science Alliance LLC 2023-06-27 /pmc/articles/PMC10300197/ /pubmed/37369603 http://dx.doi.org/10.26508/lsa.202201881 Text en © 2023 Yasuda et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Yasuda, Toru Uchiyama, Toru Watanabe, Nobuyuki Ito, Noriko Nakabayashi, Kazuhiko Mochizuki, Hideki Onodera, Masafumi Peripheral immune system modulates Purkinje cell degeneration in Niemann–Pick disease type C1 |
title | Peripheral immune system modulates Purkinje cell degeneration in Niemann–Pick disease type C1 |
title_full | Peripheral immune system modulates Purkinje cell degeneration in Niemann–Pick disease type C1 |
title_fullStr | Peripheral immune system modulates Purkinje cell degeneration in Niemann–Pick disease type C1 |
title_full_unstemmed | Peripheral immune system modulates Purkinje cell degeneration in Niemann–Pick disease type C1 |
title_short | Peripheral immune system modulates Purkinje cell degeneration in Niemann–Pick disease type C1 |
title_sort | peripheral immune system modulates purkinje cell degeneration in niemann–pick disease type c1 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300197/ https://www.ncbi.nlm.nih.gov/pubmed/37369603 http://dx.doi.org/10.26508/lsa.202201881 |
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