Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s disease
The olfactory bulb (OB) is the first processing station in the olfactory pathway. Despite smell impairment, which is considered an early event in Alzheimer’s disease (AD), little is known about the initial molecular disturbances that accompany the AD development at olfactory level. We have interroga...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/63571 |
| Acceso en línea: | https://hdl.handle.net/10171/63571 |
| Access Level: | acceso abierto |
| Palabra clave: | Alzheimer’s disease Olfactory bulb Network biology Proteomics Transcriptomics Tg2576 mice |
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Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s diseaseLachén-Montes, M. (Mercedes)|||/items/57e8086e-ac35-4404-997a-306b4118876fGonzález-Morales, A. (Andrea)|||/items/2de776be-0acf-4a28-b91e-8af3c021072aPalomino, M. (Maialen)|||/items/7db7c0ee-6503-47c9-906a-7ba5dc6e09f0Ausin, K. (Karina)|||/items/a623ce0f-3882-47be-a0f8-0fbaaffd4d32Gómez-Ochoa, M. (Marta)|||/items/12375ad3-ac81-4887-85f1-cb0209216922Zelaya, M.V. (María Victoria)|||/items/b17ebd92-1f01-4512-b71f-4f05874ca7b3Ferrer, I. (Isidro)|||/items/90a4f031-75d5-4865-a115-487f50787723Perez-Mediavilla, L.A. (Luis Alberto)|||/items/276fc9af-5d47-49eb-bf67-6d35fc210186Fernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718dSantamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8Alzheimer’s diseaseOlfactory bulbNetwork biologyProteomicsTranscriptomicsTg2576 miceThe olfactory bulb (OB) is the first processing station in the olfactory pathway. Despite smell impairment, which is considered an early event in Alzheimer’s disease (AD), little is known about the initial molecular disturbances that accompany the AD development at olfactory level. We have interrogated the time-dependent OB molecular landscape in Tg2576 AD mice prior to the appearance of neuropathological amyloid plaques (2-, and 6-month-old), using combinatorial omics analysis. The metabolic modulation induced by overproduction of human mutated amyloid precursor protein (APP) clearly differs between both time points. Besides the progressive perturbation of the APP interactome, functional network analysis unveiled an inverse regulation of downstream extracellular signal-regulated kinase (ERK1/2), and p38 mitogen-activated protein kinase (MAPK) routes in 2-month-old Tg2576 mice with respect to wild-type (WT) mice. In contrast, Akt and MAPK kinase 4 (SEK1)/ stress-activated protein kinase (SAPK) axis were parallel activated in the OB of 6-months-old-Tg2576 mice. Furthermore, a survival kinome profiling performed during the aging process (2-, 6-, and 18-month-old) revealed that olfactory APP overexpression leads to changes in the activation dynamics of protein kinase A (PKA), and SEK1/MKK4-SAPK/JNK between 6 and 18 months of age, when memory deficits appear and AD pathology is well established in transgenic mice. Interestingly, both olfactory pathways were differentially activated in a stage-dependent manner in human sporadic AD subjects with different neuropathological grading. Taken together, our data reflect the early impact of mutated APP on the OB molecular homeostasis, highlighting the progressive modulation of specific signaling pathways during the olfactory amyloidogenic pathologyFrontiers Media SADadun. Depósito Académico Digital Universidad de Navarra20222022-05-2720192019-01-0120192019-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/63571reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/635712026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s disease |
| title |
Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s disease |
| spellingShingle |
Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s disease Lachén-Montes, M. (Mercedes)|||/items/57e8086e-ac35-4404-997a-306b4118876f Alzheimer’s disease Olfactory bulb Network biology Proteomics Transcriptomics Tg2576 mice |
| title_short |
Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s disease |
| title_full |
Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s disease |
| title_fullStr |
Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s disease |
| title_full_unstemmed |
Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s disease |
| title_sort |
Early-onset molecular derangements in the olfactory bulb of Tg2576 mice: Novel insights into the stress-responsive olfactory kinase dynamics in alzheimer’s disease |
| dc.creator.none.fl_str_mv |
Lachén-Montes, M. (Mercedes)|||/items/57e8086e-ac35-4404-997a-306b4118876f González-Morales, A. (Andrea)|||/items/2de776be-0acf-4a28-b91e-8af3c021072a Palomino, M. (Maialen)|||/items/7db7c0ee-6503-47c9-906a-7ba5dc6e09f0 Ausin, K. (Karina)|||/items/a623ce0f-3882-47be-a0f8-0fbaaffd4d32 Gómez-Ochoa, M. (Marta)|||/items/12375ad3-ac81-4887-85f1-cb0209216922 Zelaya, M.V. (María Victoria)|||/items/b17ebd92-1f01-4512-b71f-4f05874ca7b3 Ferrer, I. (Isidro)|||/items/90a4f031-75d5-4865-a115-487f50787723 Perez-Mediavilla, L.A. (Luis Alberto)|||/items/276fc9af-5d47-49eb-bf67-6d35fc210186 Fernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718d Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8 |
| author |
Lachén-Montes, M. (Mercedes)|||/items/57e8086e-ac35-4404-997a-306b4118876f |
| author_facet |
Lachén-Montes, M. (Mercedes)|||/items/57e8086e-ac35-4404-997a-306b4118876f González-Morales, A. (Andrea)|||/items/2de776be-0acf-4a28-b91e-8af3c021072a Palomino, M. (Maialen)|||/items/7db7c0ee-6503-47c9-906a-7ba5dc6e09f0 Ausin, K. (Karina)|||/items/a623ce0f-3882-47be-a0f8-0fbaaffd4d32 Gómez-Ochoa, M. (Marta)|||/items/12375ad3-ac81-4887-85f1-cb0209216922 Zelaya, M.V. (María Victoria)|||/items/b17ebd92-1f01-4512-b71f-4f05874ca7b3 Ferrer, I. (Isidro)|||/items/90a4f031-75d5-4865-a115-487f50787723 Perez-Mediavilla, L.A. (Luis Alberto)|||/items/276fc9af-5d47-49eb-bf67-6d35fc210186 Fernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718d Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8 |
| author_role |
author |
| author2 |
González-Morales, A. (Andrea)|||/items/2de776be-0acf-4a28-b91e-8af3c021072a Palomino, M. (Maialen)|||/items/7db7c0ee-6503-47c9-906a-7ba5dc6e09f0 Ausin, K. (Karina)|||/items/a623ce0f-3882-47be-a0f8-0fbaaffd4d32 Gómez-Ochoa, M. (Marta)|||/items/12375ad3-ac81-4887-85f1-cb0209216922 Zelaya, M.V. (María Victoria)|||/items/b17ebd92-1f01-4512-b71f-4f05874ca7b3 Ferrer, I. (Isidro)|||/items/90a4f031-75d5-4865-a115-487f50787723 Perez-Mediavilla, L.A. (Luis Alberto)|||/items/276fc9af-5d47-49eb-bf67-6d35fc210186 Fernandez-Irigoyen, J. (Joaquín)|||/items/700f4366-d68f-4161-af03-2cac47ea718d Santamaria, E. (Enrique)|||/items/fc2c70d6-973c-4d67-8185-6c56a59477c8 |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Alzheimer’s disease Olfactory bulb Network biology Proteomics Transcriptomics Tg2576 mice |
| topic |
Alzheimer’s disease Olfactory bulb Network biology Proteomics Transcriptomics Tg2576 mice |
| description |
The olfactory bulb (OB) is the first processing station in the olfactory pathway. Despite smell impairment, which is considered an early event in Alzheimer’s disease (AD), little is known about the initial molecular disturbances that accompany the AD development at olfactory level. We have interrogated the time-dependent OB molecular landscape in Tg2576 AD mice prior to the appearance of neuropathological amyloid plaques (2-, and 6-month-old), using combinatorial omics analysis. The metabolic modulation induced by overproduction of human mutated amyloid precursor protein (APP) clearly differs between both time points. Besides the progressive perturbation of the APP interactome, functional network analysis unveiled an inverse regulation of downstream extracellular signal-regulated kinase (ERK1/2), and p38 mitogen-activated protein kinase (MAPK) routes in 2-month-old Tg2576 mice with respect to wild-type (WT) mice. In contrast, Akt and MAPK kinase 4 (SEK1)/ stress-activated protein kinase (SAPK) axis were parallel activated in the OB of 6-months-old-Tg2576 mice. Furthermore, a survival kinome profiling performed during the aging process (2-, 6-, and 18-month-old) revealed that olfactory APP overexpression leads to changes in the activation dynamics of protein kinase A (PKA), and SEK1/MKK4-SAPK/JNK between 6 and 18 months of age, when memory deficits appear and AD pathology is well established in transgenic mice. Interestingly, both olfactory pathways were differentially activated in a stage-dependent manner in human sporadic AD subjects with different neuropathological grading. Taken together, our data reflect the early impact of mutated APP on the OB molecular homeostasis, highlighting the progressive modulation of specific signaling pathways during the olfactory amyloidogenic pathology |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-01-01 2019 2019-01-01 2022 2022-05-27 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/63571 |
| url |
https://hdl.handle.net/10171/63571 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Frontiers Media SA |
| publisher.none.fl_str_mv |
Frontiers Media SA |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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1869417407833964544 |
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15,300719 |