TMEM106B aggregation in neurodegenerative diseases: linking genetics to function
Abstract Background Mutations of the gene TMEM106B are risk factors for diverse neurodegenerative diseases. Previous understanding of the underlying mechanism focused on the impairment of lysosome biogenesis caused by TMEM106B loss-of-function. However, mutations in TMEM106B increase its expression...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Molecular Neurodegeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13024-023-00644-1 |
| _version_ | 1827708312043388928 |
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| author | Hai-Shan Jiao Peng Yuan Jin-Tai Yu |
| author_facet | Hai-Shan Jiao Peng Yuan Jin-Tai Yu |
| author_sort | Hai-Shan Jiao |
| collection | DOAJ |
| description | Abstract Background Mutations of the gene TMEM106B are risk factors for diverse neurodegenerative diseases. Previous understanding of the underlying mechanism focused on the impairment of lysosome biogenesis caused by TMEM106B loss-of-function. However, mutations in TMEM106B increase its expression level, thus the molecular process linking these mutations to the apparent disruption in TMEM106B function remains mysterious. Main body Recent new studies reported that TMEM106B proteins form intracellular amyloid filaments which universally exist in various neurodegenerative diseases, sometimes being the dominant form of protein aggregation. In light of these new findings, in this review we systematically examined previous efforts in understanding the function of TMEM106B in physiological and pathological conditions. We propose that TMEM106B aggregations could recruit normal TMEM106B proteins and interfere with their function. Conclusions TMEM106B mutations could lead to lysosome dysfunction by promoting the aggregation of TMEM106B and reducing these aggregations may restore lysosomal function, providing a potential therapeutic target for various neurodegenerative diseases. |
| first_indexed | 2024-03-10T17:02:50Z |
| format | Article |
| id | doaj.art-70dd9d4ae954452ebb9e5881d8d99b55 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-03-10T17:02:50Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-70dd9d4ae954452ebb9e5881d8d99b552023-11-20T10:54:52ZengBMCMolecular Neurodegeneration1750-13262023-08-0118111310.1186/s13024-023-00644-1TMEM106B aggregation in neurodegenerative diseases: linking genetics to functionHai-Shan Jiao0Peng Yuan1Jin-Tai Yu2Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityDepartment of Rehabilitation Medicine, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Huashan Hospital, Institute for Translational Brain Research, Fudan UniversityDepartment of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan UniversityAbstract Background Mutations of the gene TMEM106B are risk factors for diverse neurodegenerative diseases. Previous understanding of the underlying mechanism focused on the impairment of lysosome biogenesis caused by TMEM106B loss-of-function. However, mutations in TMEM106B increase its expression level, thus the molecular process linking these mutations to the apparent disruption in TMEM106B function remains mysterious. Main body Recent new studies reported that TMEM106B proteins form intracellular amyloid filaments which universally exist in various neurodegenerative diseases, sometimes being the dominant form of protein aggregation. In light of these new findings, in this review we systematically examined previous efforts in understanding the function of TMEM106B in physiological and pathological conditions. We propose that TMEM106B aggregations could recruit normal TMEM106B proteins and interfere with their function. Conclusions TMEM106B mutations could lead to lysosome dysfunction by promoting the aggregation of TMEM106B and reducing these aggregations may restore lysosomal function, providing a potential therapeutic target for various neurodegenerative diseases.https://doi.org/10.1186/s13024-023-00644-1TMEM106BAmyloid fibrilsAggregationNeurodegenerationLysosomeTherapeutics |
| spellingShingle | Hai-Shan Jiao Peng Yuan Jin-Tai Yu TMEM106B aggregation in neurodegenerative diseases: linking genetics to function Molecular Neurodegeneration TMEM106B Amyloid fibrils Aggregation Neurodegeneration Lysosome Therapeutics |
| title | TMEM106B aggregation in neurodegenerative diseases: linking genetics to function |
| title_full | TMEM106B aggregation in neurodegenerative diseases: linking genetics to function |
| title_fullStr | TMEM106B aggregation in neurodegenerative diseases: linking genetics to function |
| title_full_unstemmed | TMEM106B aggregation in neurodegenerative diseases: linking genetics to function |
| title_short | TMEM106B aggregation in neurodegenerative diseases: linking genetics to function |
| title_sort | tmem106b aggregation in neurodegenerative diseases linking genetics to function |
| topic | TMEM106B Amyloid fibrils Aggregation Neurodegeneration Lysosome Therapeutics |
| url | https://doi.org/10.1186/s13024-023-00644-1 |
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