Involvement of glucosamine 6 phosphate isomerase 2 (GNPDA2) overproduction in beta-amyloid- and Tau P301L-driven pathomechanisms

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dc.contributor.authorLachén Montes, Mercedes
dc.contributor.authorCartas Cejudo, Paz
dc.contributor.authorCortés, Adriana
dc.contributor.authorAnaya-Cubero, Elena
dc.contributor.authorPeral, Erika
dc.contributor.authorAusín, Karina
dc.contributor.authorDíaz-Peña, Ramón
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2024-08-12T13:03:53Z
dc.date.available2024-08-12T13:03:53Z
dc.date.issued2024
dc.date.updated2024-08-12T12:51:46Z
dc.description.abstractAlzheimer’s disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine- or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas of AD subjects. However, the biological role of GNPDA2 in neurodegeneration remains unknown. Using mass spectrometry, multiple GNPDA2 interactors were identified in human nasal epithelial cells (NECs) mainly involved in intraciliary transport. Moreover, GNPDA2 overexpression induced an increment in NEC proliferation rates, accompanied by transcriptomic alterations in Type II interferon signaling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slowdown in the proliferative capacity in parallel with a disruption in protein processing. The proteomic characterization of Tau-P301L transgenic zebrafish embryos demonstrated that GNPDA2 overexpression interfered with collagen biosynthesis and RNA/protein processing, without inducing additional changes in axonal outgrowth defects or neuronal cell death. In humans, a significant increase in serum GNPDA2 levels was observed across multiple neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed dementia and amyotrophic lateral sclerosis) (n = 215). These data shed new light on GNPDA2-dependent mechanisms associated with the neurodegenerative process beyond the hexosamine route.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 J.F.-I. and E.S. and the Department of Economic and Business Development from Government of Navarra (Ref. 0011-1411-2020-000028 and 0011-1411-2023-000028 to E.S.).
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dc.format.mimetypeapplication/zipen
dc.identifier.citationLachén-Montes M., Cartas-Cejudo P., Cortés A., Anaya-Cubero E., Peral E., Ausín K., Díaz-Peña R., Fernández-Irigoyen J., Santamaría E. (2024) Involvement of glucosamine 6 phosphate isomerase 2 (GNPDA2) overproduction in beta-amyloid- and Tau P301L-driven pathomechanisms. Biomolecules, 14(4), 1-21. https://doi.org/10.3390/biom14040394.
dc.identifier.doi10.3390/biom14040394
dc.identifier.issn2218-273X
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/50694
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofBiomolecules 2024, 14(4), 394
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/Gobierno de Navarra//0011-1411-2020-000028/
dc.relation.projectIDinfo:eu-repo/grantAgreement/Gobierno de Navarra//0011-1411-2023-000028/
dc.relation.publisherversionhttps://doi.org/10.3390/biom14040394
dc.rights© 2024 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectGNPDA2en
dc.subjectNeurodegenerationen
dc.subjectOlfactionen
dc.subjectZebrafishen
dc.titleInvolvement of glucosamine 6 phosphate isomerase 2 (GNPDA2) overproduction in beta-amyloid- and Tau P301L-driven pathomechanismsen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
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