Functional Genomics Reveals Dysregulation of Cortical Olfactory Receptors in Parkinson Disease: Novel Putative Chemoreceptors in the Human Brain
| العنوان: | Functional Genomics Reveals Dysregulation of Cortical Olfactory Receptors in Parkinson Disease: Novel Putative Chemoreceptors in the Human Brain |
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| المؤلفون: | Belén Ansoleaga, Jesús Moreno, Agatha Schlüter, Benjamín Torrejón-Escribano, Aurora Pujol, Isidre Ferrer, Margarita Carmona, Paula Garcia-Esparcia, Stefano Gustincich |
| المصدر: | Journal of Neuropathology & Experimental Neurology; Vol 72 |
| بيانات النشر: | Oxford University Press (OUP), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Adenylyl cyclase 3, Cerebral cortex, Olfactory re- ceptors, Parkinson disease, Protein G > olf, Taste receptors, UDP- glucuronosyltransferase, Substantia nigra, Olfaction, Biology, Olfactory Receptor Neurons, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Settore BIO/13 - Biologia Applicata, medicine, Humans, Receptor, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Protein G > olf, Genomics, Taste receptors, General Medicine, Human brain, Middle Aged, Cerebral cortex, Chemoreceptor Cells, Parkinson disease, medicine.anatomical_structure, Neurology, Frontal lobe, Adenylyl cyclase 3, Olfactory re- ceptors, TAS2R10, Female, Neurology (clinical), Signal transduction, Neuroscience, 030217 neurology & neurosurgery, UDP- glucuronosyltransferase |
| الوصف: | Parkinson disease (PD) is no longer considered a complex motor disorder but rather a systemic disease with variable nonmotor deficits that may include impaired olfaction, depression, mood and sleep disorders, and altered cortical function. Increasing evidence indicates that multiple metabolic defects occur in regions outside the substantia nigra, including the cerebral cortex, even at premotor stages of the disease. We investigated changes in gene expression in the frontal cortex in PD patient brains using a transcriptomics approach. Functional genomics analysis indicated that cortical olfactory receptors (ORs) and taste receptors (TASRs) are altered in PD patients. Olfactory receptors OR2L13, OR1E1, OR2J3, OR52L1, and OR11H1 and taste receptors TAS2R5 and TAS2R50 were downregulated, but TAS2R10 and TAS2R13 were upregulated at premotor and parkinsonian stages in the frontal cortex area 8 in PD patient brains. Furthermore, we present novel evidence that, in addition to the ORs, obligate downstream components of OR function adenylyl cyclase 3 and olfactory G protein (Gαolf), OR transporters, receptor transporter proteins 1 and 2 and receptor expression enhancing protein 1, and OR xenobiotic removing UDP-glucuronosyltransferase 1 family polypeptide A6 are widely expressed in neurons of the cerebral cortex and other regions of the adult human brain. Together, these findings support the concept that ORs and TASRs in the cerebral cortex may have novel physiologic functions that are affected in PD patients. |
| تدمد: | 1554-6578 0022-3069 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d4f543070dc4b1dbb01b26a0f7847afTest https://doi.org/10.1097/nen.0b013e318294fd76Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7d4f543070dc4b1dbb01b26a0f7847af |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15546578 00223069 |
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