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
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