ReviewPost screenPotential therapeutic effects of odorants through their ectopic receptors in pigmented cells

- Expression of olfactory GPCRs outside the olfactory epithelium is demonstrated.
- Odorants can represent a new challenge for developing neuroactive drugs.
- Ectopic ORs link pigmentation disorders to neurodegenerative diseases.
- A potential role of OR521E2, OR2AT4 and VN1R1 ectopic ORs is proposed.

Several olfactory receptors (ORs) have been characterized outside the olfactory neuroepithelium in neuronal and non-neuronal tissues, where they were implicated in the recognition of diverse chemical signals. ORs have been found to regulate melanogenesis in skin melanocytes, and OR expression has been found in the human brain nigrostriatal dopaminergic neurons, where production of melanin occurs as neuromelanin and can change with age; OR expression is downregulated in Parkinson's disease. Therefore, we propose several odorants as new functional ligands to ORs expressed in non-olfactory pigmented cells as dopaminergic neurons and melanocytes, where, by acting on cAMP-induced melanin production, they could help to counteract melanogenic and neurodegenerative dysfunctions, including melanoma and Parkinson's disease.