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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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