Cellular rejuvenation protects neurons from inflammation-mediated cell death
Summary: In multiple sclerosis (MS), inflammation of the central nervous system results in demyelination, neuroaxonal injury, and cell death. However, the molecular signals responsible for injury and cell death in neurons are not fully characterized. Here, we profile the transcriptome of retinal gan...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000695 |
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| author | Sienna S. Drake Abdulshakour Mohammadnia Aliyah Zaman Christine Gianfelice Kali Heale Adam M.R. Groh Elizabeth M.-L. Hua Matthew A. Hintermayer Yuancheng Ryan Lu David Gosselin Stephanie Zandee Alexandre Prat Jo Anne Stratton David A. Sinclair Alyson E. Fournier |
| author_facet | Sienna S. Drake Abdulshakour Mohammadnia Aliyah Zaman Christine Gianfelice Kali Heale Adam M.R. Groh Elizabeth M.-L. Hua Matthew A. Hintermayer Yuancheng Ryan Lu David Gosselin Stephanie Zandee Alexandre Prat Jo Anne Stratton David A. Sinclair Alyson E. Fournier |
| author_sort | Sienna S. Drake |
| collection | DOAJ |
| description | Summary: In multiple sclerosis (MS), inflammation of the central nervous system results in demyelination, neuroaxonal injury, and cell death. However, the molecular signals responsible for injury and cell death in neurons are not fully characterized. Here, we profile the transcriptome of retinal ganglion cells (RGCs) in experimental autoimmune encephalomyelitis (EAE) mice. Pathway analysis identifies a transcriptional signature reminiscent of aged RGCs with some senescent features, with a comparable signature present in neurons from patients with MS. This is supported by immunostaining demonstrating alterations to the nuclear envelope, modifications in chromatin marks, and accumulation of DNA damage. Transduction of RGCs with an Oct4-Sox2-Klf4 adeno-associated virus (AAV) to rejuvenate the transcriptome enhances RGC survival in EAE and improves visual acuity. Collectively, these data reveal an aging-like phenotype in neurons under pathological neuroinflammation and support the possibility that rejuvenation therapies or senotherapeutic agents could offer a direct avenue for neuroprotection in neuroimmune disorders. |
| format | Article |
| id | doaj-art-dc551825215a4820839086a057877738 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-dc551825215a4820839086a0578777382025-02-12T05:31:00ZengElsevierCell Reports2211-12472025-02-01442115298Cellular rejuvenation protects neurons from inflammation-mediated cell deathSienna S. Drake0Abdulshakour Mohammadnia1Aliyah Zaman2Christine Gianfelice3Kali Heale4Adam M.R. Groh5Elizabeth M.-L. Hua6Matthew A. Hintermayer7Yuancheng Ryan Lu8David Gosselin9Stephanie Zandee10Alexandre Prat11Jo Anne Stratton12David A. Sinclair13Alyson E. Fournier14Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, CanadaDepartment of Genetics, Bavatnik Institute, Harvard Medical School, Boston, MA 02115, USADepartment of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V4G2, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, Canada; Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X0A9, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC H2X0A9, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, CanadaDepartment of Genetics, Bavatnik Institute, Harvard Medical School, Boston, MA 02115, USADepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, Canada; Corresponding authorSummary: In multiple sclerosis (MS), inflammation of the central nervous system results in demyelination, neuroaxonal injury, and cell death. However, the molecular signals responsible for injury and cell death in neurons are not fully characterized. Here, we profile the transcriptome of retinal ganglion cells (RGCs) in experimental autoimmune encephalomyelitis (EAE) mice. Pathway analysis identifies a transcriptional signature reminiscent of aged RGCs with some senescent features, with a comparable signature present in neurons from patients with MS. This is supported by immunostaining demonstrating alterations to the nuclear envelope, modifications in chromatin marks, and accumulation of DNA damage. Transduction of RGCs with an Oct4-Sox2-Klf4 adeno-associated virus (AAV) to rejuvenate the transcriptome enhances RGC survival in EAE and improves visual acuity. Collectively, these data reveal an aging-like phenotype in neurons under pathological neuroinflammation and support the possibility that rejuvenation therapies or senotherapeutic agents could offer a direct avenue for neuroprotection in neuroimmune disorders.http://www.sciencedirect.com/science/article/pii/S2211124725000695CP: Neuroscience |
| spellingShingle | Sienna S. Drake Abdulshakour Mohammadnia Aliyah Zaman Christine Gianfelice Kali Heale Adam M.R. Groh Elizabeth M.-L. Hua Matthew A. Hintermayer Yuancheng Ryan Lu David Gosselin Stephanie Zandee Alexandre Prat Jo Anne Stratton David A. Sinclair Alyson E. Fournier Cellular rejuvenation protects neurons from inflammation-mediated cell death Cell Reports CP: Neuroscience |
| title | Cellular rejuvenation protects neurons from inflammation-mediated cell death |
| title_full | Cellular rejuvenation protects neurons from inflammation-mediated cell death |
| title_fullStr | Cellular rejuvenation protects neurons from inflammation-mediated cell death |
| title_full_unstemmed | Cellular rejuvenation protects neurons from inflammation-mediated cell death |
| title_short | Cellular rejuvenation protects neurons from inflammation-mediated cell death |
| title_sort | cellular rejuvenation protects neurons from inflammation mediated cell death |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000695 |
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