The brain’s sixth sense: ectopic olfactory receptors as modulators of neuroinflammation

About
Olfactory receptors constitute the largest family of G protein-coupled receptors, yet they remain among the most enigmatic sensory receptors in biology. Traditionally understood as molecular detectors of odorants in the olfactory epithelium, these receptors are now known to be expressed in many non-olfactory tissues, including the central nervous system. This ectopic expression raises a fundamental question: what do olfactory receptors do when they are not involved in smell?

In this talk, I will discuss the biological and conceptual challenges posed by olfactory receptors, emphasizing why they differ from many other receptor families and why their functional interpretation outside the olfactory system remains complex. When expressed ectopically, olfactory receptors do not mediate odor perception. Instead, they may act as chemosensory elements capable of detecting endogenous or environmental ligands within specific tissue contexts. In the brain, outside the canonical olfactory pathway, this possibility suggests that olfactory receptors may contribute to a previously underappreciated form of molecular sensing — a potential “sixth sense” of the brain.

Special attention will be given to their possible role in neuroinflammation. Our recent results show differential expression of two olfactory receptors in microglia depending on cellular state, with distinct patterns observed between resting and activated microglia. In addition, images illustrating the expression of OR51E2 in different regions of the brain will be presented, supporting the idea that their distribution is not random and may be linked to region-specific functions. These findings suggest that specific olfactory receptors may participate in the detection, regulation, or modulation of inflammatory processes in the central nervous system.
Together with emerging evidence from other studies, our data support the idea that ectopic olfactory receptors deserve deeper investigation as functional players in brain physiology and pathology. Understanding which endogenous agonists activate these receptors, how their signaling pathways operate in glial cells, and whether they influence neuroinflammatory responses may open new perspectives in neuroscience. Moreover, because neuroinflammation is a common component of many neurological and neurodegenerative diseases, ectopic olfactory receptors may represent unexplored therapeutic targets. This talk will therefore propose that olfactory receptors in the brain should no longer be considered molecular curiosities, but rather candidate sensors and modulators of neuroimmune communication.
 

Bio
Prof. Rafael Franco is a Full Professor of Biochemistry and Molecular Biology at the University of Barcelona, where he leads the Molecular Neurobiology Laboratory. His career has been marked by pioneering contributions to the molecular understanding of G-protein-coupled receptors (GPCRs) and receptor-receptor interactions. In recent years, his group has been at the forefront of applying metabolomics to human body fluids, developing advanced protocols for metabolomics data normalization and biomarker discovery, and addressing patient stratification using multi-omics and machine learning approaches. These studies bridge analytical chemistry, systems biology, and personalized medicine, contributing to the identification of disease-specific metabolic signatures in neurological and metabolic disorders.

Hosted by PI Ana Isabel Rodríguez Pérez. Cell and Molecular Neurobiology of Parkinson's Disease Group, CiMUS

Certificates of attendance will be provided upon request at cimus.xestion [at] usc.es (cimus[dot]xestion[at]usc[dot]es). Please enter your name and surname on the printout provided during the lecture.