β-amyloid controls altered Reelin expression and processing in Alzheimer's disease
Reelin is a glycoprotein that modulates synaptic function and plasticity in the mature brain, thereby favouring memory formation. We recently reported altered cerebral Reelin expression in Alzheimer's disease (AD). Here we demonstrate pronounced Reelin changes at protein and mRNA levels in the...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2010-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996109003489 |
| _version_ | 1831583054275018752 |
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| author | Arancha Botella-López Inmaculada Cuchillo-Ibáñez Tiziana Cotrufo Su San Mok Qiao-Xin Li María-Sagrario Barquero Mara Dierssen Eduardo Soriano Javier Sáez-Valero |
| author_facet | Arancha Botella-López Inmaculada Cuchillo-Ibáñez Tiziana Cotrufo Su San Mok Qiao-Xin Li María-Sagrario Barquero Mara Dierssen Eduardo Soriano Javier Sáez-Valero |
| author_sort | Arancha Botella-López |
| collection | DOAJ |
| description | Reelin is a glycoprotein that modulates synaptic function and plasticity in the mature brain, thereby favouring memory formation. We recently reported altered cerebral Reelin expression in Alzheimer's disease (AD). Here we demonstrate pronounced Reelin changes at protein and mRNA levels in the frontal cortex in adult Down's syndrome (DS), where the extra copy of chromosome 21 leads to overexpression of β-amyloid. In cortical extracts of fetal DS samples we detected increased levels of the full-length Reelin and the 310-kDa fragment. Overexpression of mutant human amyloid precursor protein also led to an increase in levels of Reelin fragments in Tg2576 transgenic mice for human β-amyloid. Finally, in vitro Aβ42 treatment of SH-SY5Y neuroblastoma cells led to increased Reelin levels. An altered pattern of Reelin glycosylation was detected in extracts from the frontal cortex of AD patients and in Aβ42-treated SH-SY5Y cells, supporting the notion that β-amyloid triggers altered Reelin processing. These results provide evidence that Reelin expression and processing is altered in several amyloid conditions. |
| first_indexed | 2024-12-17T20:35:27Z |
| format | Article |
| id | doaj.art-117caed6d1c54abf8badd8c518a80386 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T20:35:27Z |
| publishDate | 2010-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-117caed6d1c54abf8badd8c518a803862022-12-21T21:33:28ZengElsevierNeurobiology of Disease1095-953X2010-03-01373682691β-amyloid controls altered Reelin expression and processing in Alzheimer's diseaseArancha Botella-López0Inmaculada Cuchillo-Ibáñez1Tiziana Cotrufo2Su San Mok3Qiao-Xin Li4María-Sagrario Barquero5Mara Dierssen6Eduardo Soriano7Javier Sáez-Valero8Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, E-03550, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, E-03550, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), SpainCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain; IRB-Barcelona, Parc Cientific de Barcelona, and Department of Cell Biology, University of Barcelona, E-08028, SpainDepartment of Pathology, The University of Melbourne, VIC 3010, Australia; The Mental Health Research Institute of Victoria, Parkville, VIC 3052, AustraliaDepartment of Pathology, The University of Melbourne, VIC 3010, Australia; The Mental Health Research Institute of Victoria, Parkville, VIC 3052, AustraliaDepartamento Neurología, Hospital Clínico San Carlos, Madrid, SpainGenes and Disease Program, Genomic Regulation Center (CRG), Pompeu Fabra University, Barcelona Biomedical Research Park (PRBB), and CIBER de Enfermedades Raras (CIBERER), Barcelona, E-08003, SpainCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain; IRB-Barcelona, Parc Cientific de Barcelona, and Department of Cell Biology, University of Barcelona, E-08028, SpainInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, E-03550, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain; Corresponding author. Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Av. Ramón y Cajal s/n, E-03550 Sant Joan d'Alacant, Spain. Fax: +34 965919561.Reelin is a glycoprotein that modulates synaptic function and plasticity in the mature brain, thereby favouring memory formation. We recently reported altered cerebral Reelin expression in Alzheimer's disease (AD). Here we demonstrate pronounced Reelin changes at protein and mRNA levels in the frontal cortex in adult Down's syndrome (DS), where the extra copy of chromosome 21 leads to overexpression of β-amyloid. In cortical extracts of fetal DS samples we detected increased levels of the full-length Reelin and the 310-kDa fragment. Overexpression of mutant human amyloid precursor protein also led to an increase in levels of Reelin fragments in Tg2576 transgenic mice for human β-amyloid. Finally, in vitro Aβ42 treatment of SH-SY5Y neuroblastoma cells led to increased Reelin levels. An altered pattern of Reelin glycosylation was detected in extracts from the frontal cortex of AD patients and in Aβ42-treated SH-SY5Y cells, supporting the notion that β-amyloid triggers altered Reelin processing. These results provide evidence that Reelin expression and processing is altered in several amyloid conditions.http://www.sciencedirect.com/science/article/pii/S0969996109003489Alzheimer's diseaseDown's syndromeAmyloidReelinGlycoproteinCerebral cortex |
| spellingShingle | Arancha Botella-López Inmaculada Cuchillo-Ibáñez Tiziana Cotrufo Su San Mok Qiao-Xin Li María-Sagrario Barquero Mara Dierssen Eduardo Soriano Javier Sáez-Valero β-amyloid controls altered Reelin expression and processing in Alzheimer's disease Neurobiology of Disease Alzheimer's disease Down's syndrome Amyloid Reelin Glycoprotein Cerebral cortex |
| title | β-amyloid controls altered Reelin expression and processing in Alzheimer's disease |
| title_full | β-amyloid controls altered Reelin expression and processing in Alzheimer's disease |
| title_fullStr | β-amyloid controls altered Reelin expression and processing in Alzheimer's disease |
| title_full_unstemmed | β-amyloid controls altered Reelin expression and processing in Alzheimer's disease |
| title_short | β-amyloid controls altered Reelin expression and processing in Alzheimer's disease |
| title_sort | β amyloid controls altered reelin expression and processing in alzheimer s disease |
| topic | Alzheimer's disease Down's syndrome Amyloid Reelin Glycoprotein Cerebral cortex |
| url | http://www.sciencedirect.com/science/article/pii/S0969996109003489 |
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