Olfactory Receptors as New Targets for Human Pathologies: from Molecular Mechanisms to Potential Pharmacological Modulation

The olfactory system is involved in the detection and processing of odour signals. In humans, the sense of olfaction has a significant influence on day-to-day behaviour and quality of life, playing a critical role in reproductive and neuroendocrine regulation. Olfactory detection begins in the nasal olfactory structures and proceeds to the first central station for olfactory processing, namely the olfactory bulb (OB). The OB is an extension of the brain, representing the first sensory structure for direct contact with sensory stimuli and air environmental pathogens. The olfactory epithelium (OE) is an avascular pseudostratified epithelium integrating neuronal and non-neuronal cells. The olfactory sensory neurons (OSNs), that house specific odorant receptor proteins, namely olfactory G-protein-associated receptors [olfactory receptors (ORs)], are bipolar neurons with dendritic filaments projected into the mucosal cavity and axons that, through the cribriform plate, synapse on mitral cells of the OB. During the aging process, the number of OSNs decreases because the OE is gradually replaced by the respiratory epithelium. Although OR expression was initially hypothesized to be restricted to the OSNs, an ecnomotopic expression has been identified, including different cell types and organs. Of note, ecnomotopic ORs have been reported to exert important regulatory functions in homeostasis and disease statues, such as atherosclerosis, triglyceride metabolism, hepatic lipid accumulation, glucose regulation, obesity and cancer growth. Moreover, olfactory impairment has been detected in diverse neurodegenerative disorders as well as in diabetic and obese patients. This Research Topic aims to gather pre-clinical and clinical studies on alternative therapeutic approaches and new drug design focusing on the modulation of the olfactory pathway. Furthermore, we encourage contributions exploring the impact of compounds with established pharmacological proprieties on the olfactory system with the aim of including olfactory impairment as a sensitive biomarker to predict the risk of developing neuro and metabolic disorders.In this Research Topic we welcome original research articles, clinical studies and reviews addressing but not limited to:• Olfactory disfunction and neurodegenerative disordersExperimental and clinical evidence showing how the accuracy of diagnosis will help in exploring combinatorial therapeutic approaches and slow down disease progression.• Ecnomotopic ORs and lipid/glucose metabolismClinical studies showing that saturated fatty acids and terpenes/terpenoids may be novel therapeutic treatments of diseases characterized by dysregulation in glucose and lipid metabolism.• Olfactory system and immune responseExperimental and clinical studies investigating the role of already characterized or new anti-inflammatory/immunomodulatory drugs in the olfactory detection and processing.• Olfactory pathway and microbiotaExperimental studies showing the involvement of the microbiota in maintaining functional homeostasis of the olfactory system and how prebiotic/probiotics/synbiotics/postbiotics may help. Topic editors: Cinzia Parolini, Amedeo Amedei, Thomas Heinbockel Source: https://www.frontiersin.org/research-topics/80189/olfactory-receptors-as-new-targets-for-human-pathologies-from-molecular-mechanisms-to-potential-pharmacological-modulation