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Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy

CSF1R-related leukoencephalopathy is an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by colony stimulating factor 1 receptor (CSF1R) gene mutations. The disease has a global distribution and currently has no cure. Individuals with CSF1R-related leukoencephalopathy...

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Autores principales: Han, Jinming, Sarlus, Heela, Wszolek, Zbigniew K., Karrenbauer, Virginija Danylaité, Harris, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720517/
https://www.ncbi.nlm.nih.gov/pubmed/33287883
http://dx.doi.org/10.1186/s40478-020-01093-3
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author Han, Jinming
Sarlus, Heela
Wszolek, Zbigniew K.
Karrenbauer, Virginija Danylaité
Harris, Robert A.
author_facet Han, Jinming
Sarlus, Heela
Wszolek, Zbigniew K.
Karrenbauer, Virginija Danylaité
Harris, Robert A.
author_sort Han, Jinming
collection PubMed
description CSF1R-related leukoencephalopathy is an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by colony stimulating factor 1 receptor (CSF1R) gene mutations. The disease has a global distribution and currently has no cure. Individuals with CSF1R-related leukoencephalopathy variably present clinical symptoms including cognitive impairment, progressive neuropsychiatric and motor symptoms. CSF1R is predominantly expressed on microglia within the central nervous system (CNS), and thus CSF1R-related leukoencephalopathy is now classified as a CNS primary microgliopathy. This urgent unmet medical need could potentially be addressed by using microglia-based immunotherapies. With the rapid recent progress in the experimental microglial research field, the replacement of an empty microglial niche following microglial depletion through either conditional genetic approaches or pharmacological therapies (CSF1R inhibitors) is being studied. Furthermore, hematopoietic stem cell transplantation offers an emerging means of exchanging dysfunctional microglia with the aim of reducing brain lesions, relieving clinical symptoms and prolonging the life of patients with CSF1R-related leukoencephalopathy. This review article introduces recent advances in microglial biology and CSF1R-related leukoencephalopathy. Potential therapeutic strategies by replacing microglia in order to improve the quality of life of CSF1R-related leukoencephalopathy patients will be presented.
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spelling pubmed-77205172020-12-07 Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy Han, Jinming Sarlus, Heela Wszolek, Zbigniew K. Karrenbauer, Virginija Danylaité Harris, Robert A. Acta Neuropathol Commun Review CSF1R-related leukoencephalopathy is an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by colony stimulating factor 1 receptor (CSF1R) gene mutations. The disease has a global distribution and currently has no cure. Individuals with CSF1R-related leukoencephalopathy variably present clinical symptoms including cognitive impairment, progressive neuropsychiatric and motor symptoms. CSF1R is predominantly expressed on microglia within the central nervous system (CNS), and thus CSF1R-related leukoencephalopathy is now classified as a CNS primary microgliopathy. This urgent unmet medical need could potentially be addressed by using microglia-based immunotherapies. With the rapid recent progress in the experimental microglial research field, the replacement of an empty microglial niche following microglial depletion through either conditional genetic approaches or pharmacological therapies (CSF1R inhibitors) is being studied. Furthermore, hematopoietic stem cell transplantation offers an emerging means of exchanging dysfunctional microglia with the aim of reducing brain lesions, relieving clinical symptoms and prolonging the life of patients with CSF1R-related leukoencephalopathy. This review article introduces recent advances in microglial biology and CSF1R-related leukoencephalopathy. Potential therapeutic strategies by replacing microglia in order to improve the quality of life of CSF1R-related leukoencephalopathy patients will be presented. BioMed Central 2020-12-07 /pmc/articles/PMC7720517/ /pubmed/33287883 http://dx.doi.org/10.1186/s40478-020-01093-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Han, Jinming
Sarlus, Heela
Wszolek, Zbigniew K.
Karrenbauer, Virginija Danylaité
Harris, Robert A.
Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy
title Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy
title_full Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy
title_fullStr Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy
title_full_unstemmed Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy
title_short Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy
title_sort microglial replacement therapy: a potential therapeutic strategy for incurable csf1r-related leukoencephalopathy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720517/
https://www.ncbi.nlm.nih.gov/pubmed/33287883
http://dx.doi.org/10.1186/s40478-020-01093-3
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