PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases
Abstract Dysregulated lipid metabolism in microglia represents a hallmark of neuroinflammation and is often observed in a variety of neurodegenerative diseases. The exact molecular mechanisms underlying the induction of altered lipid homeostasis and how it contributes to neurodegeneration remain to...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08272-9 |
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| _version_ | 1849434155461378048 |
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| author | Yiyue Shi Wenyu Hou Bei Li Caihong Zhu |
| author_facet | Yiyue Shi Wenyu Hou Bei Li Caihong Zhu |
| author_sort | Yiyue Shi |
| collection | DOAJ |
| description | Abstract Dysregulated lipid metabolism in microglia represents a hallmark of neuroinflammation and is often observed in a variety of neurodegenerative diseases. The exact molecular mechanisms underlying the induction of altered lipid homeostasis and how it contributes to neurodegeneration remain to be deciphered. Progranulin (PGRN) is a lysosomal glycoprotein encoded by GRN. Loss-of-function mutations or variants of GRN have been linked to various neurodegenerative diseases. PGRN has recently been identified as a regulator of lipid droplet formation in microglia. Additionally, PGRN has been reported to interact with various molecules to modulate lysosomal lipid metabolism, including glycerolipids and sphingolipids in neurons. Hence, PGRN deficiency-mediated lipid dysregulation may represent a significant contributing factor to the neuroinflammation and the pathogenesis of related neurodegenerative diseases. Understanding how PGRN regulates lipid metabolism is crucial for developing therapeutic strategies to restore lipid homeostasis in microglia and mitigate neuroinflammation, thus offering hope for effective treatments to combat these neurodegenerative disorders in the future. |
| format | Article |
| id | doaj-art-b5d9f99c28524989ac4fcbff7ec1ebbe |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-b5d9f99c28524989ac4fcbff7ec1ebbe2025-08-20T03:26:47ZengNature PortfolioCommunications Biology2399-36422025-06-018111210.1038/s42003-025-08272-9PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseasesYiyue Shi0Wenyu Hou1Bei Li2Caihong Zhu3School of Basic Medical Sciences, Fudan UniversitySchool of Basic Medical Sciences, Fudan UniversitySchool of Basic Medical Sciences, Fudan UniversitySchool of Basic Medical Sciences, Fudan UniversityAbstract Dysregulated lipid metabolism in microglia represents a hallmark of neuroinflammation and is often observed in a variety of neurodegenerative diseases. The exact molecular mechanisms underlying the induction of altered lipid homeostasis and how it contributes to neurodegeneration remain to be deciphered. Progranulin (PGRN) is a lysosomal glycoprotein encoded by GRN. Loss-of-function mutations or variants of GRN have been linked to various neurodegenerative diseases. PGRN has recently been identified as a regulator of lipid droplet formation in microglia. Additionally, PGRN has been reported to interact with various molecules to modulate lysosomal lipid metabolism, including glycerolipids and sphingolipids in neurons. Hence, PGRN deficiency-mediated lipid dysregulation may represent a significant contributing factor to the neuroinflammation and the pathogenesis of related neurodegenerative diseases. Understanding how PGRN regulates lipid metabolism is crucial for developing therapeutic strategies to restore lipid homeostasis in microglia and mitigate neuroinflammation, thus offering hope for effective treatments to combat these neurodegenerative disorders in the future.https://doi.org/10.1038/s42003-025-08272-9 |
| spellingShingle | Yiyue Shi Wenyu Hou Bei Li Caihong Zhu PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases Communications Biology |
| title | PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases |
| title_full | PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases |
| title_fullStr | PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases |
| title_full_unstemmed | PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases |
| title_short | PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases |
| title_sort | pgrn as an emerging regulator of lipid metabolism in neurodegenerative diseases |
| url | https://doi.org/10.1038/s42003-025-08272-9 |
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