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FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment
Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system (CNS) that is characterized by myelin damage, followed by axonal and ultimately neuronal loss, which has been found to be associated with mitophagy. The etiology and pathology of MS remain elusive. H...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10640650/ https://www.ncbi.nlm.nih.gov/pubmed/37952053 http://dx.doi.org/10.1038/s41419-023-06260-7 |
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author | Sun, Xingzong Qian, Menghan Li, Hongliang Wang, Lei Zhao, Yunjie Yin, Min Dai, Lili Bao, Hongkun |
author_facet | Sun, Xingzong Qian, Menghan Li, Hongliang Wang, Lei Zhao, Yunjie Yin, Min Dai, Lili Bao, Hongkun |
author_sort | Sun, Xingzong |
collection | PubMed |
description | Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system (CNS) that is characterized by myelin damage, followed by axonal and ultimately neuronal loss, which has been found to be associated with mitophagy. The etiology and pathology of MS remain elusive. However, the role of FK506 binding protein 5 (FKBP5, also called FKBP51), a newly identified gene associated with MS, in the progression of the disease has not been well defined. Here, we observed that the progress of myelin loss and regeneration in Fkbp5(ko) mice treated with demyelination for the same amount of time was significantly slower than that in wild-type mice, and that mitophagy plays an important regulatory role in this process. To investigate the mechanism, we discovered that the levels of FKBP5 protein were greatly enhanced in the CNS of cuprizone (CPZ) mice and the myelin-denuded environment stimulates significant activation of the PINK1/Parkin-mediated mitophagy, in which the important regulator, PPAR-γ, is critically regulated by FKBP5. This study reveals the role of FKBP5 in regulating a dynamic pathway of natural restorative regulation of mitophagy through PPAR-γ in pathological demyelinating settings, which may provide potential targets for the treatment of demyelinating diseases. |
format | Online Article Text |
id | pubmed-10640650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106406502023-11-11 FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment Sun, Xingzong Qian, Menghan Li, Hongliang Wang, Lei Zhao, Yunjie Yin, Min Dai, Lili Bao, Hongkun Cell Death Dis Article Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system (CNS) that is characterized by myelin damage, followed by axonal and ultimately neuronal loss, which has been found to be associated with mitophagy. The etiology and pathology of MS remain elusive. However, the role of FK506 binding protein 5 (FKBP5, also called FKBP51), a newly identified gene associated with MS, in the progression of the disease has not been well defined. Here, we observed that the progress of myelin loss and regeneration in Fkbp5(ko) mice treated with demyelination for the same amount of time was significantly slower than that in wild-type mice, and that mitophagy plays an important regulatory role in this process. To investigate the mechanism, we discovered that the levels of FKBP5 protein were greatly enhanced in the CNS of cuprizone (CPZ) mice and the myelin-denuded environment stimulates significant activation of the PINK1/Parkin-mediated mitophagy, in which the important regulator, PPAR-γ, is critically regulated by FKBP5. This study reveals the role of FKBP5 in regulating a dynamic pathway of natural restorative regulation of mitophagy through PPAR-γ in pathological demyelinating settings, which may provide potential targets for the treatment of demyelinating diseases. Nature Publishing Group UK 2023-11-11 /pmc/articles/PMC10640650/ /pubmed/37952053 http://dx.doi.org/10.1038/s41419-023-06260-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sun, Xingzong Qian, Menghan Li, Hongliang Wang, Lei Zhao, Yunjie Yin, Min Dai, Lili Bao, Hongkun FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment |
title | FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment |
title_full | FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment |
title_fullStr | FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment |
title_full_unstemmed | FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment |
title_short | FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment |
title_sort | fkbp5 activates mitophagy by ablating ppar-γ to shape a benign remyelination environment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10640650/ https://www.ncbi.nlm.nih.gov/pubmed/37952053 http://dx.doi.org/10.1038/s41419-023-06260-7 |
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