{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:14:30Z","timestamp":1788408870969,"version":"build-2803163510"},"reference-count":104,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","award":["MEXT-JSPS 17K08884"],"award-info":[{"award-number":["MEXT-JSPS 17K08884"]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PT17\/0019\/009"],"award-info":[{"award-number":["PT17\/0019\/009"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-110356RB-I00"],"award-info":[{"award-number":["PID2019-110356RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Department of Economic and Business Development from Government of Navarra","doi-asserted-by":"publisher","award":["0011-1411-2020-000028"],"award-info":[{"award-number":["0011-1411-2020-000028"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The 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\u2019s 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\u2013\/\u2013 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.<\/jats:p>","DOI":"10.1021\/acs.jproteome.0c00452","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T11:53:41Z","timestamp":1605268421000},"page":"4826-4843","source":"Crossref","is-referenced-by-count":10,"title":["Smelling the Dark\nProteome: Functional Characterization\nof PITH Domain-Containing Protein 1 (C1orf128) in Olfactory Metabolism"],"prefix":"10.1021","volume":"19","author":[{"given":"Mercedes","family":"Lache\u0301n-Montes","sequence":"first","affiliation":[{"name":"Universidad Pu\u0301blica de Navarra (UPNA) , , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]},{"name":"Universidad Pu\u0301blica de Navarra (UPNA) , , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]},{"name":"IdiSNA, Navarra Institute for Health Research , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naroa","family":"Mendizuri","sequence":"additional","affiliation":[{"name":"Universidad Pu\u0301blica de Navarra (UPNA) , , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]},{"name":"Universidad Pu\u0301blica de Navarra (UPNA) , , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]},{"name":"IdiSNA, Navarra Institute for Health Research , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Ausi\u0301n","sequence":"additional","affiliation":[{"name":"Universidad Pu\u0301blica de Navarra (UPNA) , , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]},{"name":"Universidad Pu\u0301blica de Navarra (UPNA) , , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]},{"name":"IdiSNA, Navarra Institute for Health Research , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Pe\u0301rez-Mediavilla","sequence":"additional","affiliation":[{"name":"IdiSNA, Navarra Institute for Health Research , Irunlarrea 3 , ,","place":["Pamplona, Spain, 31008"]},{"name":"University of Navarra , , ,","place":["Pamplona, Spain, 31008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikel","family":"Azkargorta","sequence":"additional","affiliation":[{"name":"Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII , Bizkaia Science and Technology Park , ,","place":["Derio, Spain, 48160"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibon","family":"Iloro","sequence":"additional","affiliation":[{"name":"Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII , Bizkaia Science and Technology Park , ,","place":["Derio, Spain, 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,","place":["Madrid, Spain, 28029"]},{"name":"University of Barcelona , , ,","place":["Hospitalet de Llobregat, Spain, 08908"]},{"name":"University of Barcelona , , ,","place":["Barcelona, Spain, 08007"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Neurosciences Research Program, IMIM (Hospital del Mar Medical Research Institute) , , ,","place":["Barcelona, Spain, 08003"]},{"name":"Pompeu Fabra University (CEXS-UPF) , , ,","place":["Barcelona, Spain, 08002"]},{"name":"Universitat Auto\u0300noma de Barcelona , , ,","place":["Cerdanyola del Valle\u0300s, Spain, 08193"]},{"name":"CIBER de Fisiopatologi\u0301a de la Obesidad y Nutricio\u0301n (CB06\/03) , , ,","place":["Madrid, Spain, 28029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Robledo","sequence":"additional","affiliation":[{"name":"Neurosciences Research Program, IMIM (Hospital del Mar Medical 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