Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease.
Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease.
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DOI：
10.3389/fnagi.2016.00163
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发表时间：
2016
影响因子：
4.8
通讯作者：
Gustincich S
中科院分区：
文献类型：
--
作者：
Ferrer I;Garcia-Esparcia P;Carmona M;Carro E;Aronica E;Kovacs GG;Grison A;Gustincich S
嗅觉受体（OR）和下游功能性信号分子腺苷酸环化酶3（AC 3）、嗅觉G蛋白α亚基（Gαolf）、OR转运体受体转运蛋白1和2（RTP 1和RTP 2）、受体表达增强蛋白1（REEP 1）和UDP-葡萄糖醛酸转移酶（UGT）在人和鼠中枢神经系统（CNS）的神经元中表达。体外研究表明，这些受体对外部刺激有反应，因此具有功能性。然而，OR与气味的检测没有直接关系。从血液、脑脊液、邻近的局部神经元和神经胶质细胞、通过细胞外间隙的远端细胞递送的几种分子以及细胞自身的自我调节内部稳态可以被假定为可能的配体。此外，嗅上皮外的单个神经元表达多种受体，并且嗅上皮和脑神经元的转录调控机制可能不同。OR基因表达在几种神经退行性疾病中改变，包括帕金森病（PD）、阿尔茨海默病（AD）、进行性核上性麻痹（PSP）和散发性克雅氏病（sCJD）亚型MM 1和VV 2，具有疾病、区域和亚型特异性模式。在精神分裂症患者的前额皮质中也观察到基因表达的改变，氯丙嗪治疗对其有主要但非全部的影响。初步的平行观察也显示了味觉受体（TASRs）的存在，主要是苦味家族，在哺乳动物的大脑中，其功能与味觉无关。脑中的TASRs在神经退行性疾病中也受到异常调节。这些开创性的观察指出，需要进一步研究哺乳动物大脑中的OR和TASRs化学感受器。
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.