RIPK1 expression and inhibition in tauopathies: implications for neuroinflammation and neuroprotection
Tauopathies are a group of neurodegenerative diseases characterized by the alteration/aggregation of TAU protein. One of the main challenges of these diseases is that they have neither biomarkers nor pharmacological targets to stop the neurodegenerative process. Apart from the neurodegenerative proc...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2024.1530809/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832584984900141056 |
|---|---|
| author | Ignacio Silva-Llanes Ignacio Silva-Llanes Ignacio Silva-Llanes Enrique Madruga Enrique Madruga Ana Martínez Ana Martínez Isabel Lastres-Becker Isabel Lastres-Becker Isabel Lastres-Becker Isabel Lastres-Becker |
| author_facet | Ignacio Silva-Llanes Ignacio Silva-Llanes Ignacio Silva-Llanes Enrique Madruga Enrique Madruga Ana Martínez Ana Martínez Isabel Lastres-Becker Isabel Lastres-Becker Isabel Lastres-Becker Isabel Lastres-Becker |
| author_sort | Ignacio Silva-Llanes |
| collection | DOAJ |
| description | Tauopathies are a group of neurodegenerative diseases characterized by the alteration/aggregation of TAU protein. One of the main challenges of these diseases is that they have neither biomarkers nor pharmacological targets to stop the neurodegenerative process. Apart from the neurodegenerative process, tauopathies are also characterized by a chronic low-grade neuroinflammation process, where the receptor-interacting protein kinase 1 (RIPK1) protein plays an essential role. Our research aimed to explore the role of RIPK1 in various tauopathies. We examined mouse models of frontotemporal dementia (FTD), as well as brain tissue samples from patients with progressive supranuclear palsy (PSP), a primary form of 4R tauopathy, and Alzheimer’s disease (AD), which is considered a secondary tauopathy. Our findings show elevated levels of RIPK1 mRNA levels across various forms of tauopathies, in both mouse models and human tissue samples associated with primary and secondary TAU-related disorders. Furthermore, we investigated the potential of using a RIPK1 inhibitor, known as GSK2982772, in a mouse model as a novel treatment strategy for FTD. The data showed that GSK2982772 treatment effectively reduced the reactive astrocyte response triggered by TAUP301L overexpression. However, this RIPK1 inhibitor failed to protect against the neurodegeneration caused by elevated TAUP301L levels in the hippocampal region. These results suggest that although inhibiting RIPK1 activity may help reduce TAU-related astrogliosis in the brain, the complexity of the inflammatory pathways involved could explain the absence of neuroprotective effects against TAU-induced neurodegeneration. |
| format | Article |
| id | doaj-art-341a4799d810441383fd7679ee7633ec |
| institution | Kabale University |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj-art-341a4799d810441383fd7679ee7633ec2025-01-27T06:41:02ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-01-011810.3389/fnins.2024.15308091530809RIPK1 expression and inhibition in tauopathies: implications for neuroinflammation and neuroprotectionIgnacio Silva-Llanes0Ignacio Silva-Llanes1Ignacio Silva-Llanes2Enrique Madruga3Enrique Madruga4Ana Martínez5Ana Martínez6Isabel Lastres-Becker7Isabel Lastres-Becker8Isabel Lastres-Becker9Isabel Lastres-Becker10Department of Biochemistry, School of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, SpainInstituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, SpainInstituto de Investigaciones Biomédicas “Sols-Morreale” UAM-CSIC, Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainCentro de Investigaciones Biológicas Margarita Salas (CSIC), Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartment of Biochemistry, School of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, SpainInstituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, SpainInstituto de Investigaciones Biomédicas “Sols-Morreale” UAM-CSIC, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainTauopathies are a group of neurodegenerative diseases characterized by the alteration/aggregation of TAU protein. One of the main challenges of these diseases is that they have neither biomarkers nor pharmacological targets to stop the neurodegenerative process. Apart from the neurodegenerative process, tauopathies are also characterized by a chronic low-grade neuroinflammation process, where the receptor-interacting protein kinase 1 (RIPK1) protein plays an essential role. Our research aimed to explore the role of RIPK1 in various tauopathies. We examined mouse models of frontotemporal dementia (FTD), as well as brain tissue samples from patients with progressive supranuclear palsy (PSP), a primary form of 4R tauopathy, and Alzheimer’s disease (AD), which is considered a secondary tauopathy. Our findings show elevated levels of RIPK1 mRNA levels across various forms of tauopathies, in both mouse models and human tissue samples associated with primary and secondary TAU-related disorders. Furthermore, we investigated the potential of using a RIPK1 inhibitor, known as GSK2982772, in a mouse model as a novel treatment strategy for FTD. The data showed that GSK2982772 treatment effectively reduced the reactive astrocyte response triggered by TAUP301L overexpression. However, this RIPK1 inhibitor failed to protect against the neurodegeneration caused by elevated TAUP301L levels in the hippocampal region. These results suggest that although inhibiting RIPK1 activity may help reduce TAU-related astrogliosis in the brain, the complexity of the inflammatory pathways involved could explain the absence of neuroprotective effects against TAU-induced neurodegeneration.https://www.frontiersin.org/articles/10.3389/fnins.2024.1530809/fullneuroinflammationTAURIPK1neurodegenerationAlzheimer’s disease (AD)progressive supranuclear palsy (PSP) |
| spellingShingle | Ignacio Silva-Llanes Ignacio Silva-Llanes Ignacio Silva-Llanes Enrique Madruga Enrique Madruga Ana Martínez Ana Martínez Isabel Lastres-Becker Isabel Lastres-Becker Isabel Lastres-Becker Isabel Lastres-Becker RIPK1 expression and inhibition in tauopathies: implications for neuroinflammation and neuroprotection Frontiers in Neuroscience neuroinflammation TAU RIPK1 neurodegeneration Alzheimer’s disease (AD) progressive supranuclear palsy (PSP) |
| title | RIPK1 expression and inhibition in tauopathies: implications for neuroinflammation and neuroprotection |
| title_full | RIPK1 expression and inhibition in tauopathies: implications for neuroinflammation and neuroprotection |
| title_fullStr | RIPK1 expression and inhibition in tauopathies: implications for neuroinflammation and neuroprotection |
| title_full_unstemmed | RIPK1 expression and inhibition in tauopathies: implications for neuroinflammation and neuroprotection |
| title_short | RIPK1 expression and inhibition in tauopathies: implications for neuroinflammation and neuroprotection |
| title_sort | ripk1 expression and inhibition in tauopathies implications for neuroinflammation and neuroprotection |
| topic | neuroinflammation TAU RIPK1 neurodegeneration Alzheimer’s disease (AD) progressive supranuclear palsy (PSP) |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2024.1530809/full |
| work_keys_str_mv | AT ignaciosilvallanes ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT ignaciosilvallanes ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT ignaciosilvallanes ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT enriquemadruga ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT enriquemadruga ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT anamartinez ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT anamartinez ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT isabellastresbecker ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT isabellastresbecker ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT isabellastresbecker ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection AT isabellastresbecker ripk1expressionandinhibitionintauopathiesimplicationsforneuroinflammationandneuroprotection |