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The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia
The neurobiology of schizophrenia is multifactorial, comprising the dysregulation of several biochemical pathways and molecules. This research proposes a peripheral biomarker for schizophrenia that involves the second extracellular loop of norepinephrine transporter (NEText), the tropomyosin recepto...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395201/ https://www.ncbi.nlm.nih.gov/pubmed/34445205 http://dx.doi.org/10.3390/ijms22168499 |
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author | Rodrigues-Amorim, Daniela Iglesias-Martínez-Almeida, Marta Rivera-Baltanás, Tania Fernández-Palleiro, Patricia Freiría-Martínez, Luis Rodríguez-Jamardo, Cynthia Comís-Tuche, María Vallejo-Curto, María del Carmen Álvarez-Ariza, María López-García, Marta de las Heras, Elena García-Caballero, Alejandro Olivares, Jose Manuel Spuch, Carlos |
author_facet | Rodrigues-Amorim, Daniela Iglesias-Martínez-Almeida, Marta Rivera-Baltanás, Tania Fernández-Palleiro, Patricia Freiría-Martínez, Luis Rodríguez-Jamardo, Cynthia Comís-Tuche, María Vallejo-Curto, María del Carmen Álvarez-Ariza, María López-García, Marta de las Heras, Elena García-Caballero, Alejandro Olivares, Jose Manuel Spuch, Carlos |
author_sort | Rodrigues-Amorim, Daniela |
collection | PubMed |
description | The neurobiology of schizophrenia is multifactorial, comprising the dysregulation of several biochemical pathways and molecules. This research proposes a peripheral biomarker for schizophrenia that involves the second extracellular loop of norepinephrine transporter (NEText), the tropomyosin receptor kinase C (TrkC), and the neurotrophin-3 (NT-3) in T cells. The study of NEText, NT-3, and TrkC was performed in T cells and plasma extracted from peripheral blood of 54 patients with schizophrenia and 54 healthy controls. Levels of NT-3, TrkC, and NET were significantly lower in plasma and T cells of patients compared to healthy controls. Co-immunoprecipitation (co-IPs) showed protein interactions with Co-IP NEText–NT-3 and Co-IP NEText–TrkC. Computational modelling of protein–peptide docking by CABS-dock provided a medium–high accuracy model for NT-3–NEText (4.6935 Å) and TrkC–NEText (2.1365 Å). In summary, immunocomplexes reached statistical relevance in the T cells of the control group contrary to the results obtained with schizophrenia. The reduced expression of NT-3, TrkC, and NET, and the lack of molecular complexes in T cells of patients with schizophrenia may lead to a peripheral dysregulation of intracellular signaling pathways and an abnormal reuptake of norepinephrine (NE) by NET. This peripheral molecular biomarker underlying schizophrenia reinforces the role of neurotrophins, and noradrenergic and immune systems in the pathophysiology of schizophrenia. |
format | Online Article Text |
id | pubmed-8395201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83952012021-08-28 The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia Rodrigues-Amorim, Daniela Iglesias-Martínez-Almeida, Marta Rivera-Baltanás, Tania Fernández-Palleiro, Patricia Freiría-Martínez, Luis Rodríguez-Jamardo, Cynthia Comís-Tuche, María Vallejo-Curto, María del Carmen Álvarez-Ariza, María López-García, Marta de las Heras, Elena García-Caballero, Alejandro Olivares, Jose Manuel Spuch, Carlos Int J Mol Sci Article The neurobiology of schizophrenia is multifactorial, comprising the dysregulation of several biochemical pathways and molecules. This research proposes a peripheral biomarker for schizophrenia that involves the second extracellular loop of norepinephrine transporter (NEText), the tropomyosin receptor kinase C (TrkC), and the neurotrophin-3 (NT-3) in T cells. The study of NEText, NT-3, and TrkC was performed in T cells and plasma extracted from peripheral blood of 54 patients with schizophrenia and 54 healthy controls. Levels of NT-3, TrkC, and NET were significantly lower in plasma and T cells of patients compared to healthy controls. Co-immunoprecipitation (co-IPs) showed protein interactions with Co-IP NEText–NT-3 and Co-IP NEText–TrkC. Computational modelling of protein–peptide docking by CABS-dock provided a medium–high accuracy model for NT-3–NEText (4.6935 Å) and TrkC–NEText (2.1365 Å). In summary, immunocomplexes reached statistical relevance in the T cells of the control group contrary to the results obtained with schizophrenia. The reduced expression of NT-3, TrkC, and NET, and the lack of molecular complexes in T cells of patients with schizophrenia may lead to a peripheral dysregulation of intracellular signaling pathways and an abnormal reuptake of norepinephrine (NE) by NET. This peripheral molecular biomarker underlying schizophrenia reinforces the role of neurotrophins, and noradrenergic and immune systems in the pathophysiology of schizophrenia. MDPI 2021-08-07 /pmc/articles/PMC8395201/ /pubmed/34445205 http://dx.doi.org/10.3390/ijms22168499 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rodrigues-Amorim, Daniela Iglesias-Martínez-Almeida, Marta Rivera-Baltanás, Tania Fernández-Palleiro, Patricia Freiría-Martínez, Luis Rodríguez-Jamardo, Cynthia Comís-Tuche, María Vallejo-Curto, María del Carmen Álvarez-Ariza, María López-García, Marta de las Heras, Elena García-Caballero, Alejandro Olivares, Jose Manuel Spuch, Carlos The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia |
title | The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia |
title_full | The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia |
title_fullStr | The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia |
title_full_unstemmed | The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia |
title_short | The Role of the Second Extracellular Loop of Norepinephrine Transporter, Neurotrophin-3 and Tropomyosin Receptor Kinase C in T Cells: A Peripheral Biomarker in the Etiology of Schizophrenia |
title_sort | role of the second extracellular loop of norepinephrine transporter, neurotrophin-3 and tropomyosin receptor kinase c in t cells: a peripheral biomarker in the etiology of schizophrenia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395201/ https://www.ncbi.nlm.nih.gov/pubmed/34445205 http://dx.doi.org/10.3390/ijms22168499 |
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