Τίτλος:
Cerebrospinal fluid synaptic proteins as useful biomarkers in tyrosine hydroxylase deficiency
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine biosynthesis and a cause of early parkinsonism. Two clinical phenotypes have been described. Type "B": early onset severe encephalopathy; type "A": later onset, less severe and better response to L-dopa. We aimed to study the expression of several key dopaminergic and gabaergic synaptic proteins in the cerebrospinal fluid (CSF) of a series of patients with TH deficiency and their possible relation with the clinical phenotype and response to L-DOPA.Dopamine transporter (DAT), D2-receptor and vesicular monoamine transporter (VMAT2) were measured in the CSF of 10 subjects with TH deficiency by Western blot analysis. In 3 patients, data of pre- and post-treatment with L-DOPA were available, and in one of them, GABA vesicular transporter was determined. Results were compared to an age-matched control population.The concentration of D2-receptors in CSF was significantly higher in patients with TH deficiency than in controls. Similarly, DAT and vesicular monoamine transporter type 2 were up-regulated. Studies performed before L-DOPA, and on L-DOPA therapy showed a paradoxical response with D2 receptor expression increase as L-Dopa doses and homovanillic concentration gradually raised in a B phenotype patient. The opposite results were found in two patients with A phenotype. However, this is a very small sample, and further studies are needed to conclude robust differences between phenotypes.Synaptic proteins are detectable in the CSF and their quantification can be useful for understanding the pathophysiology of neurotransmitter defects and potentially to adjust and personalize treatments in the future. © 2014 Elsevier Inc.
Συγγραφείς:
Ortez, C.
Duarte, S.T.
Ormazábal, A.
Serrano, M.
Pérez, A.
Pons, R.
Pineda, M.
Yapici, Z.
Fernández-Álvarez, E.
Domingo-Jiménez, R.
De Castro, P.
Artuch, R.
García-Cazorla, A.
Περιοδικό:
Molecular Genetics and Metabolism
Εκδότης:
Academic Press Inc.
Λέξεις-κλειδιά:
4 aminobutyric acid; biological marker; dopamine 2 receptor; dopamine transporter; levodopa; tyrosine 3 monooxygenase; vesicular monoamine transporter; vesicular monoamine transporter 2; biological marker; dopamine 2 receptor; dopamine transporter; DRD2 protein, human; levodopa; SLC18A2 protein, human; tyrosine 3 monooxygenase; vesicular monoamine transporter, adolescent; adult; Article; cerebrospinal fluid; child; clinical article; controlled study; enzyme deficiency; female; GABAergic transmission; human; inborn error of metabolism; infant; male; molecular weight; optical density; preschool child; tyrosine hydroxylase deficiency; upregulation; Western blotting; young adult; cerebrospinal fluid; deficiency; Dystonic Disorders; gene expression; metabolism; newborn; phenotype, Adolescent; Adult; Biological Markers; Child; Child, Preschool; Dopamine Plasma Membrane Transport Proteins; Dystonic Disorders; Female; Gene Expression; Humans; Infant, Newborn; Levodopa; Male; Phenotype; Receptors, Dopamine D2; Tyrosine 3-Monooxygenase; Vesicular Monoamine Transport Proteins; Young Adult
DOI:
10.1016/j.ymgme.2014.10.014
