DYSREGULATION OF BRAIN OLFACTORY AND TASTE RECEPTORS IN AD, PSP AND CJD, AND AD-RELATED MODEL
DYSREGULATION OF BRAIN OLFACTORY AND TASTE RECEPTORS IN AD, PSP AND CJD, AND AD-RELATED MODEL
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DOI：
10.1016/j.neuroscience.2013.06.034
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发表时间：
2013-09-17
期刊：
影响因子：
3.3
通讯作者：
Ferrer, I.
中科院分区：
文献类型：
--
作者：
Ansoleaga, B.;Garcia-Esparcia, P.;Ferrer, I.
最近，我们已经显示了新的化学感受器的表达相应的嗅觉受体（OR）和味觉受体（TASR）的家庭在人脑中。我们还发现帕金森病患者大脑皮层中的OR和TASRs失调。本研究证明了小鼠大脑皮层中存在OR mRNA和OR信号转导腺苷酸环化酶3（ADYLC 3）和嗅觉G蛋白（Gnal）的强制性下游组分的mRNA。在阿尔茨海默病（AD）的内嗅皮层和额叶皮层中发现了选定OR和TASRs的失调，其梯度与Braak和Braak分期一致;在进行性核上性麻痹的终末期额叶皮层中;以及在克雅氏病亚型PRNP（MM 1）密码子129处的甲硫氨酸/甲硫氨酸和PRNP（VV 2）密码子129处的缬氨酸/缬氨酸中发现了额叶皮层和小脑中选定OR和TASRs的失调。在用作AD模型的APP/PS1致突变小鼠中也发现了随着疾病进展而改变的OR、ADYLC 3和Gnal mRNA表达。这些孤儿受体的功能尚不清楚，但可能与响应未鉴定配体的细胞信号传导途径有关。漂移的变化，无论是下调或上调，失调的基因，表明中央OR和TASRs是容易受到杂色的神经退行性疾病与皮质参与，并改变表达的OR和TASRs不仅仅是神经元损失的反映，而是调制的病理反应。(C)2013年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Recently, we have shown the expression of novel chemoreceptors corresponding to the olfactory receptor (OR) and taste receptor (TASR) families in the human brain. We have also shown dysregulation of ORs and TASRs in the cerebral cortex in Parkinson's disease. The present study demonstrates the presence of OR mRNA and mRNA of obligated downstream components of OR signaling adenylyl cyclase 3 (ADYLC3) and olfactory G protein (Gnal) in the cerebral cortex of the mouse. Dysregulation of selected ORs and TASRs has been found in the entorhinal cortex and frontal cortex in Alzheimer's disease (AD) in a gradient compatible with Braak and Braak staging; frontal cortex in terminal stages of Progressive Supranuclear Palsy; and frontal cortex and cerebellum in Creutzfeldt-Jakob disease subtypes methionine/methionine at codon 129 of PRNP (MM1) and valine/valine at codon 129 of PRNP (VV2). Altered OR, ADYLC3 and Gnal mRNA expression with disease progression has also been found in APP/PS1 transfenic mice, used as a model of AD. The function of these orphan receptors is not known, but probably related to cell signaling pathways responding to unidentified ligands. Variability in the drift, either down- or up-regulation, of dysregulated genes, suggests that central ORs and TASRs are vulnerable to variegated neurodegenerative diseases with cortical involvement, and that altered expression of ORs and TASRs is not a mere reflection of neuronal loss but rather a modulated pathological response. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.