Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative
Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity) pl...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fnagi.2018.00140/full |
| _version_ | 1819083902191403008 |
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| author | Victoria Navarro Victoria Navarro Victoria Navarro Elisabeth Sanchez-Mejias Elisabeth Sanchez-Mejias Sebastian Jimenez Sebastian Jimenez Sebastian Jimenez Clara Muñoz-Castro Clara Muñoz-Castro Clara Muñoz-Castro Raquel Sanchez-Varo Raquel Sanchez-Varo Jose C. Davila Jose C. Davila Marisa Vizuete Marisa Vizuete Marisa Vizuete Antonia Gutierrez Antonia Gutierrez Javier Vitorica Javier Vitorica Javier Vitorica |
| author_facet | Victoria Navarro Victoria Navarro Victoria Navarro Elisabeth Sanchez-Mejias Elisabeth Sanchez-Mejias Sebastian Jimenez Sebastian Jimenez Sebastian Jimenez Clara Muñoz-Castro Clara Muñoz-Castro Clara Muñoz-Castro Raquel Sanchez-Varo Raquel Sanchez-Varo Jose C. Davila Jose C. Davila Marisa Vizuete Marisa Vizuete Marisa Vizuete Antonia Gutierrez Antonia Gutierrez Javier Vitorica Javier Vitorica Javier Vitorica |
| author_sort | Victoria Navarro |
| collection | DOAJ |
| description | Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity) play a central role. In other degenerative processes, such as Alzheimer’s disease (AD), the role of microglia is far to be elucidated. In this “mini-review” article, we briefly highlight our recent data comparing the microglial response between amyloidogenic transgenic models, such as APP/PS1 and AD patients. Since the AD pathology could display regional heterogeneity, we focus our work at the hippocampal formation. In APP based models a prominent microglial response is triggered around amyloid-beta (Aβ) plaques. These strongly activated microglial cells could drive the AD pathology and, in consequence, could be implicated in the neurodegenerative process observed in models. On the contrary, the microglial response in human samples is, at least, partial or attenuated. This patent difference could simply reflect the lower and probably slower Aβ production observed in human hippocampal samples, in comparison with models, or could reflect the consequence of a chronic long-standing microglial activation. Beside this differential response, we also observed microglial degeneration in Braak V–VI individuals that, indeed, could compromise their normal role of surveying the brain environment and respond to the damage. This microglial degeneration, particularly relevant at the dentate gyrus, might be mediated by the accumulation of toxic soluble phospho-tau species. The consequences of this probably deficient immunological protection, observed in AD patients, are unknown. |
| first_indexed | 2024-12-21T20:39:56Z |
| format | Article |
| id | doaj.art-50ae89fd61994598be1ecd54a860d17f |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-21T20:39:56Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-50ae89fd61994598be1ecd54a860d17f2022-12-21T18:51:00ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652018-05-011010.3389/fnagi.2018.00140357752Microglia in Alzheimer’s Disease: Activated, Dysfunctional or DegenerativeVictoria Navarro0Victoria Navarro1Victoria Navarro2Elisabeth Sanchez-Mejias3Elisabeth Sanchez-Mejias4Sebastian Jimenez5Sebastian Jimenez6Sebastian Jimenez7Clara Muñoz-Castro8Clara Muñoz-Castro9Clara Muñoz-Castro10Raquel Sanchez-Varo11Raquel Sanchez-Varo12Jose C. Davila13Jose C. Davila14Marisa Vizuete15Marisa Vizuete16Marisa Vizuete17Antonia Gutierrez18Antonia Gutierrez19Javier Vitorica20Javier Vitorica21Javier Vitorica22Departamento Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Seville, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, SpainCentro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainCentro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartamento Biologia Celular, Genetica y Fisiologia, Facultad de Ciencias, Instituto de Biomedicina de Malaga (IBIMA), Universidad de Málaga, Málaga, SpainDepartamento Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Seville, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, SpainCentro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartamento Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Seville, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, SpainCentro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainCentro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartamento Biologia Celular, Genetica y Fisiologia, Facultad de Ciencias, Instituto de Biomedicina de Malaga (IBIMA), Universidad de Málaga, Málaga, SpainCentro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartamento Biologia Celular, Genetica y Fisiologia, Facultad de Ciencias, Instituto de Biomedicina de Malaga (IBIMA), Universidad de Málaga, Málaga, SpainDepartamento Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Seville, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, SpainCentro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainCentro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainDepartamento Biologia Celular, Genetica y Fisiologia, Facultad de Ciencias, Instituto de Biomedicina de Malaga (IBIMA), Universidad de Málaga, Málaga, SpainDepartamento Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Seville, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, SpainCentro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainMicroglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity) play a central role. In other degenerative processes, such as Alzheimer’s disease (AD), the role of microglia is far to be elucidated. In this “mini-review” article, we briefly highlight our recent data comparing the microglial response between amyloidogenic transgenic models, such as APP/PS1 and AD patients. Since the AD pathology could display regional heterogeneity, we focus our work at the hippocampal formation. In APP based models a prominent microglial response is triggered around amyloid-beta (Aβ) plaques. These strongly activated microglial cells could drive the AD pathology and, in consequence, could be implicated in the neurodegenerative process observed in models. On the contrary, the microglial response in human samples is, at least, partial or attenuated. This patent difference could simply reflect the lower and probably slower Aβ production observed in human hippocampal samples, in comparison with models, or could reflect the consequence of a chronic long-standing microglial activation. Beside this differential response, we also observed microglial degeneration in Braak V–VI individuals that, indeed, could compromise their normal role of surveying the brain environment and respond to the damage. This microglial degeneration, particularly relevant at the dentate gyrus, might be mediated by the accumulation of toxic soluble phospho-tau species. The consequences of this probably deficient immunological protection, observed in AD patients, are unknown.http://journal.frontiersin.org/article/10.3389/fnagi.2018.00140/fullAlzheimer diseasemicrogliaAPP modelsinflamationAbeta plaques |
| spellingShingle | Victoria Navarro Victoria Navarro Victoria Navarro Elisabeth Sanchez-Mejias Elisabeth Sanchez-Mejias Sebastian Jimenez Sebastian Jimenez Sebastian Jimenez Clara Muñoz-Castro Clara Muñoz-Castro Clara Muñoz-Castro Raquel Sanchez-Varo Raquel Sanchez-Varo Jose C. Davila Jose C. Davila Marisa Vizuete Marisa Vizuete Marisa Vizuete Antonia Gutierrez Antonia Gutierrez Javier Vitorica Javier Vitorica Javier Vitorica Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative Frontiers in Aging Neuroscience Alzheimer disease microglia APP models inflamation Abeta plaques |
| title | Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative |
| title_full | Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative |
| title_fullStr | Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative |
| title_full_unstemmed | Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative |
| title_short | Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative |
| title_sort | microglia in alzheimer s disease activated dysfunctional or degenerative |
| topic | Alzheimer disease microglia APP models inflamation Abeta plaques |
| url | http://journal.frontiersin.org/article/10.3389/fnagi.2018.00140/full |
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