The many connections of UFMylation with Alzheimer’s disease: a comprehensive review
Abstract Alzheimer’s disease (AD) is a complex neurodegenerative disorder that is characterized by the accumulation of pathologic tau and beta-amyloid proteins. UFMylation is an emerging ubiquitin-like post-translational modification that is crucial for healthy brain development. The UFM1 cascade wa...
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| Format: | Article |
| Language: | English |
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BMC
2025-06-01
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| Series: | Molecular Neurodegeneration |
| Online Access: | https://doi.org/10.1186/s13024-025-00855-8 |
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| author | Tingxiang Yan Benjamin D. Clarkson Zhenkun Lou Wolfdieter Springer Fabienne C. Fiesel |
| author_facet | Tingxiang Yan Benjamin D. Clarkson Zhenkun Lou Wolfdieter Springer Fabienne C. Fiesel |
| author_sort | Tingxiang Yan |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease (AD) is a complex neurodegenerative disorder that is characterized by the accumulation of pathologic tau and beta-amyloid proteins. UFMylation is an emerging ubiquitin-like post-translational modification that is crucial for healthy brain development. The UFM1 cascade was recently identified as a major modifier of tau aggregation in vitro and in vivo. Moreover, post-mortem AD brain shows pronounced alterations of UFMylation that are significantly associated with pathological tau, suggesting UFM1 might indeed be a modifier of human disease. However, the link between AD and UFMylation is yet to be fully explored. Interestingly, the UFMylation cascade is known to play important roles for several pathways that are known to be altered in AD, such as the DNA damage response, ER homeostasis, autophagy and the immune response. This review discusses the many connections between UFMylation with AD pathogenesis, emphasizing the role of UFMylation in these pathways and their abnormalities in AD. Understanding these connections is important to elucidate molecular mechanisms how UFM1 may impact AD and to uncover novel therapeutic strategies targeting UFMylation pathways for disease modification. |
| format | Article |
| id | doaj-art-d78b39fa15374804a717b87dc52b4b2c |
| institution | Kabale University |
| issn | 1750-1326 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj-art-d78b39fa15374804a717b87dc52b4b2c2025-08-20T03:26:43ZengBMCMolecular Neurodegeneration1750-13262025-06-0120111910.1186/s13024-025-00855-8The many connections of UFMylation with Alzheimer’s disease: a comprehensive reviewTingxiang Yan0Benjamin D. Clarkson1Zhenkun Lou2Wolfdieter Springer3Fabienne C. Fiesel4Department of Neuroscience, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Oncology, Mayo ClinicDepartment of Neuroscience, Mayo ClinicDepartment of Neuroscience, Mayo ClinicAbstract Alzheimer’s disease (AD) is a complex neurodegenerative disorder that is characterized by the accumulation of pathologic tau and beta-amyloid proteins. UFMylation is an emerging ubiquitin-like post-translational modification that is crucial for healthy brain development. The UFM1 cascade was recently identified as a major modifier of tau aggregation in vitro and in vivo. Moreover, post-mortem AD brain shows pronounced alterations of UFMylation that are significantly associated with pathological tau, suggesting UFM1 might indeed be a modifier of human disease. However, the link between AD and UFMylation is yet to be fully explored. Interestingly, the UFMylation cascade is known to play important roles for several pathways that are known to be altered in AD, such as the DNA damage response, ER homeostasis, autophagy and the immune response. This review discusses the many connections between UFMylation with AD pathogenesis, emphasizing the role of UFMylation in these pathways and their abnormalities in AD. Understanding these connections is important to elucidate molecular mechanisms how UFM1 may impact AD and to uncover novel therapeutic strategies targeting UFMylation pathways for disease modification.https://doi.org/10.1186/s13024-025-00855-8 |
| spellingShingle | Tingxiang Yan Benjamin D. Clarkson Zhenkun Lou Wolfdieter Springer Fabienne C. Fiesel The many connections of UFMylation with Alzheimer’s disease: a comprehensive review Molecular Neurodegeneration |
| title | The many connections of UFMylation with Alzheimer’s disease: a comprehensive review |
| title_full | The many connections of UFMylation with Alzheimer’s disease: a comprehensive review |
| title_fullStr | The many connections of UFMylation with Alzheimer’s disease: a comprehensive review |
| title_full_unstemmed | The many connections of UFMylation with Alzheimer’s disease: a comprehensive review |
| title_short | The many connections of UFMylation with Alzheimer’s disease: a comprehensive review |
| title_sort | many connections of ufmylation with alzheimer s disease a comprehensive review |
| url | https://doi.org/10.1186/s13024-025-00855-8 |
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