Friday, 16 February 2018 10:31

Targeting olfactory receptors by agonists, aromas, microbiota or digital scents : Myth or Reality?


The olfactory receptor (OR) is the first protein that recognizes odorants in the olfactory signal pathway and it is present in over 1,000 genes. Olfactory receptors are G protein-coupled receptors which serve important sensory functions beyond their role as odorant detectors in the olfactory epithelium. Olfactory receptors detect volatile chemicals that lead to the initial perception of smell in the brain. 

Most ORs are extensively expressed in the nasal olfactory epithelium where they perform the appropriate physiological functions that fit their location.

However, recent whole-genome sequencing shows that ORs have been found outside of the olfactory system, suggesting that ORs may play an important role in the ectopic expression of non-chemosensory tissues.

The ectopic expressions of ORs and their physiological functions have attracted more attention recently since MOR23 and testicular hOR17-4 have been found to be involved in skeletal muscle development, regeneration, and human sperm chemotaxis, respectively. Olfr1393, as a regulator of renal glucose handling, is specifically expressed in the kidney proximal tubule, which is the site of renal glucose reabsorption. Olfr1393 knockout mice exhibit urinary glucose wasting and improved glucose tolerance, despite euglycemia and normal insulin levels.

As the outermost barrier of the body, the skin is exposed to multiple environmental factors, including temperature, humidity, mechanical stress, and chemical stimuli such as odorants. Keratinocytes, the major cell type of the epidermal layer, express a variety of different sensory receptors that enable them to react to various environmental stimuli and process information in the skin. Recently, the identification of a novel type of chemoreceptors in human keratinocytes, the olfactory receptors OR2AT4, and identified Sandalore, a synthetic sandalwood odorant, as an agonist of this receptor. Sandalore induces strong Ca(2+) signals in cultured human keratinocytes, which are mediated by OR2AT4, as demonstrated by receptor knockdown experiments using RNA interference. The activation of OR2AT4 induces a cAMP-dependent pathway and phosphorylation of extracellular signal-regulated kinases (Erk1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Moreover, the long-term stimulation of keratinocytes with Sandalore positively affected cell proliferation and migration, and regeneration of keratinocyte monolayers in an in vitro wound scratch assay. OR 2AT4 is involved in human keratinocyte re-epithelialization during wound-healing processes.

The Gut Microbiota and Olfactory Receptors are one of the intriguing phenomenons. How Gut microbiota communicate with the brain, skin, kidney, liver...? How they activate OR? What kind of agonist? This is one of questions which will be discussed.

The Digital Olfaction science needs the understanding of how to activate and modulate these multi-locations ORs. Why our nose is everywhere? Can a Digital aroma activate skin OR? A multi-disciplinary collaboration is urgently needed between experts of olfactory receptors and the digital science.

Finally, a strategic question is how digital olfaction world will establish non-verbal communication between us (our Olfactory Receptors) and the artificial systems (robots, connected devices…)?


Marvin Edeas 975x975EDEAS, Marvin

University of Paris Descartes, INSERM 1016, Institut Cochin, Paris, France