Tackling the biological meaning of the human olfactory bulb dyshomeostatic proteome across neurological disorders: an integrative bioinformatic approach

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dc.contributor.authorCartas Cejudo, Paz
dc.contributor.authorLachén Montes, Mercedes
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2022-04-12T10:43:59Z
dc.date.available2022-04-12T10:43:59Z
dc.date.issued2021
dc.description.abstractOlfactory dysfunction is considered an early prodromal marker of many neurodegenerative diseases. Neuropathological changes and aberrant protein aggregates occur in the olfactory bulb (OB), triggering a tangled cascade of molecular events that is not completely understood across neurological disorders. This study aims to analyze commonalities and differences in the olfactory protein homeostasis across neurological backgrounds with different spectrums of smell dysfunction. For that, an integrative analysis was performed using OB proteomics datasets derived from subjects with Alzheimer’s disease (AD), Parkinson´s disease (PD), mixed dementia (mixD), dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD-TDP43), progressive supranuclear palsy (PSP) and amyotrophic lateral sclerosis (ALS) with respect to OB proteome data from neurologically intact controls. A total of 80% of the differential expressed protein products were potentially disease-specific whereas the remaining 20% were commonly altered across two, three or four neurological phenotypes. A multi-level bioinformatic characterization revealed a subset of potential disease-specific transcription factors responsible for the downstream effects detected at the proteome level as well as specific densely connected protein complexes targeted by several neurological phenotypes. Interestingly, common or unique pathways and biofunctions were also identified, providing novel mechanistic clues about each neurological disease at olfactory level. The analysis of olfactory epithelium, olfactory tract and primary olfactory cortical proteotypes in a multi-disease format will functionally complement the OB dyshomeostasis, increasing our knowledge about the neurodegenerative process across the olfactory axis.en
dc.description.sponsorshipThis work was funded by grants from the Spanish Ministry of Science, Innovation and Universities (Ref. PID2019-110356RB-I00/ AEI / 10.13039/501100011033 to JF-I and ES) and the Department of Economic and Business Development of the Government of Navarra (Ref. 0011-14112020-000028 to ES).The Proteomics Platform of Navarrabiomed, member of Proteored (PRB3ISCIII), was supported by grant PT17/0019/009, of the PE I+D+I 2013-2016 funded by ISCIII and FEDER to JF. The Clinical Neuroproteomics Unit of Navarrabiomed is member of the Spanish Olfactory Network (ROE) (supported by grant RED2018-102662-T funded by Spanish Ministry of Science and Innovation) and the Global Consortium for Chemosensory Research (GCCR).en
dc.format.extent16 p.
dc.format.mimetypeapplication/pdfen
dc.format.mimetypeapplication/zipen
dc.identifier.doi10.3390/ijms222111340
dc.identifier.issn1661-6596
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/42751
dc.language.isoengen
dc.publisherMDPIen
dc.relation.ispartofInternational Journal of Molecular Sciences, 22 (21), 2021en
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RED2018-102668-T/
dc.relation.publisherversionhttps://doi.org/10.3390/ijms222111340
dc.rights© 2021 by the authors. Creative Commons Attribution 4.0 Internationalen
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectNeurodegenerationen
dc.subjectOlfactory bulben
dc.subjectPathwaysen
dc.subjectProteomicsen
dc.titleTackling the biological meaning of the human olfactory bulb dyshomeostatic proteome across neurological disorders: an integrative bioinformatic approachen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublicationda1d0e22-8279-4c6c-a7c5-cef564dc9542
relation.isAuthorOfPublicationcc02d7db-8e88-40d1-81e0-834617b4849d
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relation.isAuthorOfPublication.latestForDiscoverycc02d7db-8e88-40d1-81e0-834617b4849d

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