title: Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease.
abstract: Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells' own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain.
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Hospitalet de Llobregat, University of BarcelonaBarcelona, Spain; Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)Madrid, Spain; Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de LlobregatBarcelona, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Hospitalet de Llobregat, University of BarcelonaBarcelona, Spain; Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)Madrid, Spain; Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de LlobregatBarcelona, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia-Esparcia
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Hospitalet de Llobregat, University of BarcelonaBarcelona, Spain; Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)Madrid, Spain; Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de LlobregatBarcelona, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Carmona
authors.affiliation: Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)Madrid, Spain; Neuroscience Group, Research Institute HospitalMadrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
authors.affiliation: Department of Neuropathology, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.affiliation: Institute of Neurology, Medical University of Vienna Vienna, Austria.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA), Area of Neuroscience Trieste, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Grison
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA), Area of Neuroscience Trieste, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gustincich
keywords: Alzheimer; Creutzfeldt-Jakob disease; Parkinson; brain; olfactory receptors; progressive supranuclear palsy; schizophrenia; taste receptors