Amyloid-β peptide triggers Fas-independent apoptosis and differentiation of neural progenitor cells
Amyloid-β peptide (Aβ), derived from the amyloid-β precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease and induces neuronal apoptosis. Neural progenitor cells persist in the adult mammalian brain and continue to produce new neurons throughout the life. The a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-06-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996104002785 |
| _version_ | 1824027156662976512 |
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| author | Pascal Millet Céline Silva Lages Stéphane Haïk Ewa Nowak Isabelle Allemand Christine Granotier François D. Boussin |
| author_facet | Pascal Millet Céline Silva Lages Stéphane Haïk Ewa Nowak Isabelle Allemand Christine Granotier François D. Boussin |
| author_sort | Pascal Millet |
| collection | DOAJ |
| description | Amyloid-β peptide (Aβ), derived from the amyloid-β precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease and induces neuronal apoptosis. Neural progenitor cells persist in the adult mammalian brain and continue to produce new neurons throughout the life. The aim of our study was to establish the effects of Aβ on neural progenitor cells (NPC). We found that the neurotoxic peptide Aβ25–35 induced apoptosis of both neurons and NPC in wild-type (wt) primary cortical cultures derived from mouse embryos. Contrary to neurons, NPC were also subjected to apoptosis in response to Aβ25–35 in both fas−/− and Z-VAD/fmk (the broad-spectrum caspase inhibitor)-treated wt cortical cultures indicating that Aβ triggers a Fas- and caspase-independent apoptotic pathway in NPC. Interestingly, we also show that Aβ induces neurospheres adherence and NPC neuronal differentiation. Further studies are thus needed in order to understand the role of Aβ effects on NPC in AD pathology. Understanding the mechanisms involved may also be essential for the development of new regenerative therapies in AD. |
| first_indexed | 2024-12-19T11:20:57Z |
| format | Article |
| id | doaj.art-fb9bcad3ad564f3093440883f7f4be16 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T11:20:57Z |
| publishDate | 2005-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-fb9bcad3ad564f3093440883f7f4be162022-12-21T20:23:49ZengElsevierNeurobiology of Disease1095-953X2005-06-011915765Amyloid-β peptide triggers Fas-independent apoptosis and differentiation of neural progenitor cellsPascal Millet0Céline Silva Lages1Stéphane Haïk2Ewa Nowak3Isabelle Allemand4Christine Granotier5François D. Boussin6Laboratoire de Radiopathologie, DRR/DSV, CEA, IPSC, Fontenay-aux-Roses, FranceLaboratoire de Radiopathologie, DRR/DSV, CEA, IPSC, Fontenay-aux-Roses, FranceINSERM-Equipe Avenir “Human prion diseases”, Laboratoire de Neuropathologie, IFR 70 (Neurosciences), Hôpital de la Salpêtrière, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceLaboratoire de Radiopathologie, DRR/DSV, CEA, IPSC, Fontenay-aux-Roses, FranceLaboratoire de Gamétogenèse, Apoptose et Génotoxicité, DRR/DSV, CEA, INSERM U566, CEA, Fontenay-aux-Roses, FranceLaboratoire de Radiopathologie, DRR/DSV, CEA, IPSC, Fontenay-aux-Roses, FranceLaboratoire de Radiopathologie, DRR/DSV, CEA, IPSC, Fontenay-aux-Roses, France; Corresponding author. Fax: +33 1 46 54 97 02.Amyloid-β peptide (Aβ), derived from the amyloid-β precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease and induces neuronal apoptosis. Neural progenitor cells persist in the adult mammalian brain and continue to produce new neurons throughout the life. The aim of our study was to establish the effects of Aβ on neural progenitor cells (NPC). We found that the neurotoxic peptide Aβ25–35 induced apoptosis of both neurons and NPC in wild-type (wt) primary cortical cultures derived from mouse embryos. Contrary to neurons, NPC were also subjected to apoptosis in response to Aβ25–35 in both fas−/− and Z-VAD/fmk (the broad-spectrum caspase inhibitor)-treated wt cortical cultures indicating that Aβ triggers a Fas- and caspase-independent apoptotic pathway in NPC. Interestingly, we also show that Aβ induces neurospheres adherence and NPC neuronal differentiation. Further studies are thus needed in order to understand the role of Aβ effects on NPC in AD pathology. Understanding the mechanisms involved may also be essential for the development of new regenerative therapies in AD.http://www.sciencedirect.com/science/article/pii/S0969996104002785Alzheimer's diseaseNeural progenitor cellsAmyloid peptide AβFas/CD95/Apo1NeurogenesisApoptosis |
| spellingShingle | Pascal Millet Céline Silva Lages Stéphane Haïk Ewa Nowak Isabelle Allemand Christine Granotier François D. Boussin Amyloid-β peptide triggers Fas-independent apoptosis and differentiation of neural progenitor cells Neurobiology of Disease Alzheimer's disease Neural progenitor cells Amyloid peptide Aβ Fas/CD95/Apo1 Neurogenesis Apoptosis |
| title | Amyloid-β peptide triggers Fas-independent apoptosis and differentiation of neural progenitor cells |
| title_full | Amyloid-β peptide triggers Fas-independent apoptosis and differentiation of neural progenitor cells |
| title_fullStr | Amyloid-β peptide triggers Fas-independent apoptosis and differentiation of neural progenitor cells |
| title_full_unstemmed | Amyloid-β peptide triggers Fas-independent apoptosis and differentiation of neural progenitor cells |
| title_short | Amyloid-β peptide triggers Fas-independent apoptosis and differentiation of neural progenitor cells |
| title_sort | amyloid β peptide triggers fas independent apoptosis and differentiation of neural progenitor cells |
| topic | Alzheimer's disease Neural progenitor cells Amyloid peptide Aβ Fas/CD95/Apo1 Neurogenesis Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0969996104002785 |
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