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ID 116206
Author
Lachén-Montes, Mercedes Universidad Pública de Navarra|Navarra Institute for Health Research
Mendizuri, Naroa Universidad Pública de Navarra|Navarra Institute for Health Research
Ausín, Karina Universidad Pública de Navarra|Navarra Institute for Health Research
Pérez-Mediavilla, Alberto Navarra Institute for Health Research|University of Navarra
Azkargorta, Mikel ProteoRed-ISCIII
Iloro, Ibon ProteoRed-ISCIII
Elortza, Felix ProteoRed-ISCIII
Ferrer, Isidre Bellvitge Biomedical Research Institute|Institute of Health Carlos III|University of Barcelona
de la Torre, Rafael IMIM|Pompeu Fabra University|Universitat Autònoma de Barcelona|CIBEROBN
Robledo, Patricia IMIM|Pompeu Fabra University
Fernández-Irigoyen, Joaquín Universidad Pública de Navarra|Navarra Institute for Health Research
Santamaría, Enrique Universidad Pública de Navarra|Navarra Institute for Health Research
Keywords
Human Proteome Project
olfaction
neurodegeneration
uPE1
dark proteome
PITHD1
Content Type
Journal Article
Description
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’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.
Journal Title
Journal of Proteome Research
ISSN
15353893
15353907
NCID
AA11638846
AA12442770
Publisher
ACS Publications
Volume
19
Issue
12
Start Page
4826
End Page
4843
Published Date
2020-11-13
Rights
This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
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DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences
Institute of Advanced Medical Sciences