The human olfactory cleft mucus proteome and its age-related changes

Keiichi Yoshikawa,Nithin D Adappa,Cristina Jaen,Hong Wang,Naoko Saito,Noam A Cohen,Junji Nakamura,Pamela Dalton,Mai Haneoka

doi:10.1038/s41598-018-35102-2

Abstract

Age-related decreases in olfactory sensitivity are often accompanied by a decrease in the quality of life. However, the molecular mechanisms underlying these changes are not well described. Inhaled substances including odorants are detected by sensory neurons in the olfactory cleft covered with a layer of mucus. This olfactory mucus is the first molecular machinery responsible for tissue protection and for detection of environmental odorants. Yet, little is known about the molecular identities of the actors because of the lack of information on the mucus proteome and its age-related changes. Here, we sampled human mucus from different nasal locations and from young and elderly subjects. The composition of the mucus was extensively analyzed by shotgun proteomic analysis for a vast array of proteins. We also explored correlations between the levels of each mucus proteins with the olfactory sensitivity of subjects. This analysis revealed previously unrecognized proteins with potentially important functions in olfaction. Taken together, this report describes the most comprehensive catalogue of the nasal mucus proteins to date, their positional and age-related differences, and candidate proteins associated with olfaction. This catalogue will provide fundamental information useful for future studies, such as identification of olfactory auxiliary proteins, causes of age-related declines in olfaction, and biomarkers for neurodegenerative disorders.

Highlights

Olfaction, the sense of smell, is important for daily life
We believe that the present dataset provides the most comprehensive database of the olfactory mucus proteome and its age-related changes
We identified a list of mucus proteins which accounted for the observe variability in olfactory sensitivity of our participants

Summary

Introduction

The sense of smell, is important for daily life. Odorants, toxic substances, and microorganisms are inhaled into the nasal cavity and make direct contact with the nasal mucosal layer. Mucus from the OC was compared to mucus from more anterior parts in the nasal cavity using a liquid chromatography-UV (LC-UV) spectrum[14] This analysis indicated distinct molecular compositions, likely because the mucus in the OC and that in other parts of the nose are produced by different glands. A proteome analysis was conducted, and 83 proteins in human OC mucus were identified[15] Despite these advances, considerable gaps have still remained. A previous proteomic analysis of human olfactory mucus was conducted using two-dimensional gel electrophoresis followed by MALDI-TOF-MS analysis[15] This methodology has, in most cases, been replaced by a direct analysis using shotgun proteomics, which allows identification of a much larger number of proteins with higher reproducibility[17]. This report describes the best understanding of the olfactory mucus protein composition to date, its tissue specificity, its age-related changes and candidate proteins which are involved in olfaction

Methods

Findings

Discussion

Conclusion