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dc.creatorLachén-Montes, M. (Mercedes)-
dc.creatorMendizuri, N. (Naroa)-
dc.creatorAusin, K. (Karina)-
dc.creatorPerez-Mediavilla, L.A. (Luis Alberto)-
dc.creatorAzkargorta, M. (Mikel)-
dc.creatorIloro, I. (Ibon)-
dc.creatorElortza, F. (Felix)-
dc.creatorKondo, H. (Hiroyuki)-
dc.creatorOhigashi, I. (Izumi)-
dc.creatorFerrer, I. (Isidro)-
dc.creatorTorre, R. (Rafael) de la-
dc.creatorRobledo-Ramón, P. (Patricia)-
dc.creatorFernandez-Irigoyen, J. (Joaquín)-
dc.creatorSantamaria, E. (Enrique)-
dc.date.accessioned2023-11-21T09:01:09Z-
dc.date.available2023-11-21T09:01:09Z-
dc.date.issued2020-
dc.identifier.citationLachén-Montes, M. (Mercedes); Mendizuri, N. (Naroa); Ausin, K. (Karina); et al. "Smelling the dark proteome: Functional characterization of PITH domain-containing protein 1 (C1orf128) in olfactory metabolism". Journal of proteome research. 19 (12), 2020, 4826 - 4843es_ES
dc.identifier.issn1535-3893-
dc.identifier.urihttps://hdl.handle.net/10171/67894-
dc.description.abstractThe Human Proteome Project (HPP) consortium aims to functionally characterize the dark proteome. On the basis of the relevance of olfaction in early neurodegeneration, we have analyzed the dark proteome using data mining in public resources and omics data sets derived from the human olfactory system. Multiple dark proteins localize at synaptic terminals and may be involved in amyloidopathies such as Alzheimer’s disease (AD). We have characterized the dark PITH domain-containing protein 1 (PITHD1) in olfactory metabolism using bioinformatics, proteomics, in vitro and in vivo studies, and neuropathology. PITHD1–/– mice exhibit olfactory bulb (OB) proteome changes related to synaptic transmission, cognition, and memory. OB PITHD1 expression increases with age in wild-type (WT) mice and decreases in Tg2576 AD mice at late stages. The analysis across 6 neurological disorders reveals that olfactory tract (OT) PITHD1 is specifically upregulated in human AD. Stimulation of olfactory neuroepithelial (ON) cells with PITHD1 alters the ON phosphoproteome, modifies the proliferation rate, and induces a pro-inflammatory phenotype. This workflow applied by the Spanish C-HPP and Human Brain Proteome Project (HBPP) teams across the ON-OB-OT axis can be adapted as a guidance to decipher functional features of dark proteins. Data are available via ProteomeXchange with identifiers PXD018784 and PXD021634.es_ES
dc.description.sponsorshipWe are very grateful to the patients and relatives that generously donated the brain tissue for research purposes. We are indebted to the Neurological Tissue Bank of the Biobank from the Hospital Clinic-Institut d’Investigacions Biomediques August Pi ́ i Sunyer (IDIBAPS, Barcelona) and the Neurological Tissue Bank of HUB-ICO-IDIBELL (Barcelona, Spain) for sample and data procurement. Authors thank all of the PRIDE Team for helping with the mass spectrometric data deposit in ProteomeXChange/PRIDE. CIC bioGUNE is supported by Basque Department of Industry, Tourism and Trade (Etortek and Elkartek programs), the Innovation Technology Department of the Bizkaia County; The ProteoRed-ISCIII (Grant PRB3 IPT17/0019); CIBERehd Network and Severo Ochoa Grant (SEV-2016-0644). The Clinical Neuroproteomics Unit of Navarrabiomed is a member of the Global Consortium for Chemosensory Research (GCCR) and the Spanish Olfactory Network (ROE) (supported by grant RED2018-102662-T funded by Spanish Ministry of Science and Innovation). This project is part of the HUPO Brain Proteome Project, and these results are lined up with the Spanish Initiative on the Human Proteome Project (SpHPP). This work was funded by grants from the Spanish Ministry of Science Innovation and Universities (ref. PID2019-110356RB-I00 to JFI and ES) and Department of Economic and Business Development from Government of Navarra (ref. 0011-1411-2020-000028) to ES and from MEXT-JSPS 17K08884 and Takeda Science Foundation to IO. The Proteomics Unit of Navarrabiomed is a member of Proteored (PRB3-ISCIII) and is supported by grant PT17/0019/009 to JFI, of the PE I+D+I 2013−2016 funded by ISCIII and FEDER. MLM was supported by a postdoctoral fellowship from the Public University of Navarra (UPNA).es_ES
dc.language.isoenges_ES
dc.publisherACS Publicationses_ES
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110356RB-I00/ES/ALTERACIONES PROTEOSTATICAS TEMPRANAS EN LAS ENFERMEDADES DE ALZHEIMER Y PARKINSON A NIVEL OLFATORIO: PAPEL DE GNPDA2 Y PITHD1 DURANTE EL PROCESO DE NEURODEGENERACIONes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectHuman proteome projectes_ES
dc.subjectOlfactiones_ES
dc.subjectNeurodegenerationes_ES
dc.subjectuPE1es_ES
dc.subjectDark proteomees_ES
dc.subjectPITHD1es_ES
dc.titleSmelling the dark proteome: Functional characterization of PITH domain-containing protein 1 (C1orf128) in olfactory metabolismes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.description.noteThis is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License, which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.es_ES
dc.identifier.doi10.1021/acs.jproteome.0c00452-
dadun.citation.endingPage4843es_ES
dadun.citation.number12es_ES
dadun.citation.publicationNameJournal of proteome researches_ES
dadun.citation.startingPage4826es_ES
dadun.citation.volume19es_ES
dc.identifier.pmid33185454-

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