Olfactory receptors and human diseases.

Olfaction plays a crucial role in distinguishing odors, enabling organisms to seek benefits and evade hazards. Olfactory receptors (ORs), characterized by highly variable binding pockets, facilitate the detection of diverse odorants from both external and internal environments. Nasal ORs, expressed in olfactory sensory neurons (OSNs), are critical for olfactory cognition and associated neuronal plasticity. In contrast, extra-nasal ORs, expressed in extra-olfactory tissues, detect specific chemicals and modulate cellular processes such as proliferation, migration, inflammation, and apoptosis. Aberrant OR expression or dysfunction has been implicated in numerous human diseases, including anosmia, dementia, dermatopathies, obesity, infertility, cancers, respiratory disorders, atherosclerosis and viral infections. Olfactory training, such as aromatherapy, demonstrates significant therapeutic potential for anosmia, dementia and psychological distress. Natural or synthetic odorants have been applied for promoting hair regeneration and cutaneous wound healing. Conversely, overexpression of specific ORs in cancer cells may drive tumor progression. Additionally, ORs may mediate virus-host interactions during infection, owing to their structural variability. Collectively, OR-targeted agonists and antagonists (odorants) represent promising candidates for treating OR-associated pathologies.