PXD021642

PXD021642 is an original dataset announced via ProteomeXchange.

Title	Novel protein biomarkers of monoamine metabolism defects correlate with disease severity
Description	Background: Genetic defects of monoamine neurotransmitters are rare neurological diseases amenable to treatment with variable response. They are major causes of early parkinsonism and other spectrum of movement disorders including dopa-responsive dystonia. Objectives: To conduct proteomic studies in cerebrospinal fluid (CSF) samples of patients with monoamine defects to detect biomarkers involved in pathophysiology, clinical phenotypes, and treatment response. Methods: 90 patients from diverse centers of the “International Working Group on Neurotransmitter Related Disorders” were included in the. Clinical and molecular metadata were related to the protein abundances in the CSF. Results: Concentrations of four proteins were significantly altered, detected by Mass spectrometry and confirmed by immunoassays. First, decreased levels of Apolipoprotein D were found in severe cases of aromatic L-amino acid decarboxylase deficiency. Second, low levels of Apolipoprotein H were observed in patients with the severe phenotype of tyrosine hydroxylase deficiency (THD), whereas increased concentrations of oligodendrocyte myelin glycoprotein were found in the same subset of THD patients. Third, decreased levels of Collagen6A3 were observed in treated tetrahydrobiopterin deficiency patients. Conclusion: This study, the largest cohort of patients with monoamine defects studied so far, reports the proteomic characterization of CSF and identify four novel biomarkers that bring new insights into the consequences of early dopaminergic deprivation in the developing brain. They open new possibilities to understand their role in the pathophysiology of these disorders and they may serve as potential predictors of disease severity and therapies.
HostingRepository	PRIDE
AnnounceDate	2020-11-16
AnnouncementXML	Submission_2020-11-16_14:25:24.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eduard Sabidó
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-23 02:28:19	ID requested
⏵ 1	2020-11-16 14:25:25	announced

Trist, á, n-Noguero A, Borr, à, s E, Molero-Luis M, Wassenberg T, Peters T, Verbeek MM, Willemsen M, Opladen T, Jeltsch K, Pons R, Thony B, Horvath G, Yapici Z, Friedman J, Hyland K, Agosta GE, L, ó, pez-Laso E, Artuch R, Sabid, ó E, Garc, í, a-Cazorla À, Novel Protein Biomarkers of Monoamine Metabolism Defects Correlate with Disease Severity. Mov Disord, 36(3):690-703(2021) [pubmed]

submitter keyword: monoamine metabolism defects, proteomics

Eduard Sabido
contact affiliation	CRG,UPF
contact email	eduard.sabido@crg.eu
lab head
Eduard Sabidó
contact affiliation	Centre de Regulació Genòmica
contact email	eduard.sabido@crg.cat
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021642
     1. Label: PRIDE project
     2. Name: Novel protein biomarkers of monoamine metabolism defects correlate with disease severity