Regenerating islet-derived 1α (REG-1α) protein increases tau phosphorylation in cell and animal models of tauopathies
REG-1α, a secreted protein containing a C-type lectin domain, is expressed in various organs and plays different roles in digestive system cells in physiological and pathological conditions. Like other members of the Reg family, REG-1α is expressed also in the brain where it has different functions....
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-11-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996118303516 |
| _version_ | 1818337251422109696 |
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| author | Mireille Moussaed Sylvaine Huc-Brandt Nicolas Cubedo Michele Silhol Samy Murat Marie-Christine Lebart Gabor Kovacs Jean-Michel Verdier Francoise Trousse Mireille Rossel Anne Marcilhac |
| author_facet | Mireille Moussaed Sylvaine Huc-Brandt Nicolas Cubedo Michele Silhol Samy Murat Marie-Christine Lebart Gabor Kovacs Jean-Michel Verdier Francoise Trousse Mireille Rossel Anne Marcilhac |
| author_sort | Mireille Moussaed |
| collection | DOAJ |
| description | REG-1α, a secreted protein containing a C-type lectin domain, is expressed in various organs and plays different roles in digestive system cells in physiological and pathological conditions. Like other members of the Reg family, REG-1α is expressed also in the brain where it has different functions. For instance, we previously reported that REG-1α regulates neurite outgrowth and is overexpressed during the very early stages of Alzheimer's disease (AD). However, REG-1α function in neural cells during neural degeneration remains unknown. First, REG-1α and phosphorylated tau expression were assessed in tissue sections from the hippocampus, representing neurofibrillary tangles (NFTs), from patients with AD, and from basal ganglia, representing subcortical NFTs, from patients with progressive supranuclear palsy (PSP). We found an association between REG-1α expression, tau hyperphosphorylation and NFTs in human brain samples from patients with these neurodegenerative diseases. Then, the effects of REG-1α overexpression on tau phosphorylation and axonal morphology were investigated i) in primary cultures of rat neurons that express human tau P301L and ii) in a transgenic zebrafish model of tauopathy that expresses human tau P301L. In the tau P301L cell model, REG-1α overexpression increased tau phosphorylation at the S202/T205 and S396 residues (early and late stages of abnormal phosphorylation, respectively) through the AKT/GSK3-β pathway. This effect was associated with axonal defects both in tau P301L-expressing rat neurons and zebrafish embryos. Our findings suggest a functional role for REG-1α during tauopathy development and progression and, specifically, its involvement in the modification of tau phosphorylation temporal sequence. |
| first_indexed | 2024-12-13T14:52:15Z |
| format | Article |
| id | doaj.art-04c31204824d4d58b9f8bd14238677ea |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T14:52:15Z |
| publishDate | 2018-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-04c31204824d4d58b9f8bd14238677ea2022-12-21T23:41:18ZengElsevierNeurobiology of Disease1095-953X2018-11-01119136148Regenerating islet-derived 1α (REG-1α) protein increases tau phosphorylation in cell and animal models of tauopathiesMireille Moussaed0Sylvaine Huc-Brandt1Nicolas Cubedo2Michele Silhol3Samy Murat4Marie-Christine Lebart5Gabor Kovacs6Jean-Michel Verdier7Francoise Trousse8Mireille Rossel9Anne Marcilhac10MMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, FranceMMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, FranceMMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, FranceMMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, FranceMMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, FranceMMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, FranceInstitute of Neurology, Neurodegeneration Research Group, Medical University of Vienna, Vienna, AustriaMMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, FranceMMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, FranceMMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, FranceMMDN, Univ. Montpellier, EPHE, INSERM, U1198, PSL University, Montpellier F-34095, France; Corresponding author at: INSERM U1198, Montpellier University, Place E. Bataillon, CC 105, 34095 Montpellier Cedex 05, France.REG-1α, a secreted protein containing a C-type lectin domain, is expressed in various organs and plays different roles in digestive system cells in physiological and pathological conditions. Like other members of the Reg family, REG-1α is expressed also in the brain where it has different functions. For instance, we previously reported that REG-1α regulates neurite outgrowth and is overexpressed during the very early stages of Alzheimer's disease (AD). However, REG-1α function in neural cells during neural degeneration remains unknown. First, REG-1α and phosphorylated tau expression were assessed in tissue sections from the hippocampus, representing neurofibrillary tangles (NFTs), from patients with AD, and from basal ganglia, representing subcortical NFTs, from patients with progressive supranuclear palsy (PSP). We found an association between REG-1α expression, tau hyperphosphorylation and NFTs in human brain samples from patients with these neurodegenerative diseases. Then, the effects of REG-1α overexpression on tau phosphorylation and axonal morphology were investigated i) in primary cultures of rat neurons that express human tau P301L and ii) in a transgenic zebrafish model of tauopathy that expresses human tau P301L. In the tau P301L cell model, REG-1α overexpression increased tau phosphorylation at the S202/T205 and S396 residues (early and late stages of abnormal phosphorylation, respectively) through the AKT/GSK3-β pathway. This effect was associated with axonal defects both in tau P301L-expressing rat neurons and zebrafish embryos. Our findings suggest a functional role for REG-1α during tauopathy development and progression and, specifically, its involvement in the modification of tau phosphorylation temporal sequence.http://www.sciencedirect.com/science/article/pii/S0969996118303516REG-1αTauPhosphorylationHuman brainCortical neuronsZebrafish |
| spellingShingle | Mireille Moussaed Sylvaine Huc-Brandt Nicolas Cubedo Michele Silhol Samy Murat Marie-Christine Lebart Gabor Kovacs Jean-Michel Verdier Francoise Trousse Mireille Rossel Anne Marcilhac Regenerating islet-derived 1α (REG-1α) protein increases tau phosphorylation in cell and animal models of tauopathies Neurobiology of Disease REG-1α Tau Phosphorylation Human brain Cortical neurons Zebrafish |
| title | Regenerating islet-derived 1α (REG-1α) protein increases tau phosphorylation in cell and animal models of tauopathies |
| title_full | Regenerating islet-derived 1α (REG-1α) protein increases tau phosphorylation in cell and animal models of tauopathies |
| title_fullStr | Regenerating islet-derived 1α (REG-1α) protein increases tau phosphorylation in cell and animal models of tauopathies |
| title_full_unstemmed | Regenerating islet-derived 1α (REG-1α) protein increases tau phosphorylation in cell and animal models of tauopathies |
| title_short | Regenerating islet-derived 1α (REG-1α) protein increases tau phosphorylation in cell and animal models of tauopathies |
| title_sort | regenerating islet derived 1α reg 1α protein increases tau phosphorylation in cell and animal models of tauopathies |
| topic | REG-1α Tau Phosphorylation Human brain Cortical neurons Zebrafish |
| url | http://www.sciencedirect.com/science/article/pii/S0969996118303516 |
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