RT Journal Article
T1 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
A1 Rodrigues Amorim, Daniela
A1 Iglesias Martínez Almeida, Marta
A1 Rivera Baltanás, Tania
A1 Fernández Palleiro, Patricia
A1 Freiría Martínez, Luis
A1 Rodríguez Jamardo, Cynthia
A1 Comís Tuche, María
A1 Vallejo Curto, María del Carmen
A1 Álvarez Ariza, María
A1 López García, Marta
A1 Heras, Elena de las
A1 García Caballero, Alejandro
A1 Olivares, Jose Manuel
A1 Spuch Calvar, Carlos
K1 32 Ciencias Médicas
K1 3207.11 Neuropatología
K1 3211 Psiquiatría
AB 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.
PB International Journal of Molecular Sciences
SN 14220067
YR 2021
FD 2021-08-07
LK http://hdl.handle.net/11093/2462
UL http://hdl.handle.net/11093/2462
LA eng
NO International Journal of Molecular Sciences, 22(16): 8499 (2021)
NO Fundação para a Ciência e a Tecnologia | Ref. SFRH/BD/135623/2018
DS Investigo
RD 08-sep-2024