Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases
Abstract Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosi...
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BMC
2025-03-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-025-01964-7 |
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| author | Kerry Blair Raquel Martinez-Serra Philippe Gosset Sandra M. Martín-Guerrero Gábor M. Mórotz Joseph Atherton Jacqueline C. Mitchell Andrea Markovinovic Christopher C. J. Miller |
| author_facet | Kerry Blair Raquel Martinez-Serra Philippe Gosset Sandra M. Martín-Guerrero Gábor M. Mórotz Joseph Atherton Jacqueline C. Mitchell Andrea Markovinovic Christopher C. J. Miller |
| author_sort | Kerry Blair |
| collection | DOAJ |
| description | Abstract Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). A number of studies have now demonstrated that ER-mitochondria signaling is perturbed in these diseases and there is evidence that this may be a driving mechanism in disease onset and progression. VAPB and PTPIP51 are ER-mitochondria tethering proteins; VAPB is an ER protein and PTPIP51 is an outer mitochondrial membrane protein and the two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction is disrupted in Alzheimer’s disease, Parkinson’s disease, FTD and ALS. Here we review the roles of VAPB and PTPIP51 in ER-mitochondria signaling and the mechanisms by which neurodegenerative disease insults may disrupt the VAPB-PTPIP51 interaction. |
| format | Article |
| id | doaj-art-8d2fa117b9cf4039ad17be12c36bcefb |
| institution | Kabale University |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-8d2fa117b9cf4039ad17be12c36bcefb2025-08-20T03:45:41ZengBMCActa Neuropathologica Communications2051-59602025-03-011311910.1186/s40478-025-01964-7Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseasesKerry Blair0Raquel Martinez-Serra1Philippe Gosset2Sandra M. Martín-Guerrero3Gábor M. Mórotz4Joseph Atherton5Jacqueline C. Mitchell6Andrea Markovinovic7Christopher C. J. Miller8Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonRandall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King’s College LondonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College LondonAbstract Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). A number of studies have now demonstrated that ER-mitochondria signaling is perturbed in these diseases and there is evidence that this may be a driving mechanism in disease onset and progression. VAPB and PTPIP51 are ER-mitochondria tethering proteins; VAPB is an ER protein and PTPIP51 is an outer mitochondrial membrane protein and the two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction is disrupted in Alzheimer’s disease, Parkinson’s disease, FTD and ALS. Here we review the roles of VAPB and PTPIP51 in ER-mitochondria signaling and the mechanisms by which neurodegenerative disease insults may disrupt the VAPB-PTPIP51 interaction.https://doi.org/10.1186/s40478-025-01964-7Neurodegenerative diseasesFrontotemporal dementiaAmyotrophic lateral sclerosisAlzheimer’s diseaseParkinson’s disease |
| spellingShingle | Kerry Blair Raquel Martinez-Serra Philippe Gosset Sandra M. Martín-Guerrero Gábor M. Mórotz Joseph Atherton Jacqueline C. Mitchell Andrea Markovinovic Christopher C. J. Miller Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases Acta Neuropathologica Communications Neurodegenerative diseases Frontotemporal dementia Amyotrophic lateral sclerosis Alzheimer’s disease Parkinson’s disease |
| title | Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases |
| title_full | Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases |
| title_fullStr | Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases |
| title_full_unstemmed | Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases |
| title_short | Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases |
| title_sort | structural and functional studies of the vapb ptpip51 er mitochondria tethering proteins in neurodegenerative diseases |
| topic | Neurodegenerative diseases Frontotemporal dementia Amyotrophic lateral sclerosis Alzheimer’s disease Parkinson’s disease |
| url | https://doi.org/10.1186/s40478-025-01964-7 |
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