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
Autor: | Carlos Spuch, Alejandro García-Caballero, Daniela Rodrigues-Amorim, Marta López-García, María Del Carmen Vallejo-Curto, Luis Freiría-Martínez, María Comís-Tuche, Elena de Las Heras, Patricia Fernández-Palleiro, María Álvarez-Ariza, Marta Iglesias-Martínez-Almeida, José M. Olivares, Cynthia Rodriguez-Jamardo, Tania Rivera-Baltanás |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Adult
Male medicine.medical_specialty QH301-705.5 T cells 3211 Psiquiatría Neurotrophin-3 Tropomyosin receptor kinase C Protein Structure Secondary Article Catalysis Reuptake Inorganic Chemistry Norepinephrine Immune system Neurotrophin 3 neurotrophin-3 32 Ciencias Médicas Internal medicine tropomyosin receptor kinase C medicine Humans Receptor trkC Biology (General) Physical and Theoretical Chemistry Receptor QD1-999 Molecular Biology Spectroscopy Norepinephrine Plasma Membrane Transport Proteins biology Chemistry Organic Chemistry General Medicine Middle Aged second extracellular loop of NET Computer Science Applications Molecular Docking Simulation schizophrenia Endocrinology Norepinephrine transporter nervous system biology.protein 3207.11 Neuropatología Female Biomarkers Neurotrophin medicine.drug |
Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 8499, p 8499 (2021) International Journal of Molecular Sciences Investigo. Repositorio Institucional de la Universidade de Vigo Universidade de Vigo (UVigo) Volume 22 Issue 16 |
Popis: | 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. Fundação para a Ciência e a Tecnologia | Ref. SFRH/BD/135623/2018 Instituto de Salud Carlos III | Ref. P16/00405 Instituto de Salud Carlos III | Ref. PI20/00937 Axencia Galega de Innovación | Ref. IN607B 2018/17 |
Databáze: | OpenAIRE |
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