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Peripheral upregulation of Parkinson’s disease-associated genes encoding α-synuclein, β-glucocerebrosidase, and ceramide glucosyltransferase in major depression

Due to the high comorbidity of Parkinson’s disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (SNCA), lysosomal enzyme β-glucocerebrosidase (GB...

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Main Authors: Brazdiş, Răzvan-Marius (Author) , Zimmermann, Claudia von (Author) , Lenz, Bernd (Author) , Kornhuber, Johannes (Author) , Mühle, Christiane (Author)
Format: Article (Journal)
Language:English
Published: 12 March 2024
In: International journal of molecular sciences
Year: 2024, Volume: 25, Issue: 6, Pages: 1-16
ISSN:1422-0067
DOI:10.3390/ijms25063219
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms25063219
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/25/6/3219
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Author Notes:Razvan-Marius Brazdis, Claudia von Zimmermann, Bernd Lenz, Johannes Kornhuber and Christiane Mühle
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Summary:Due to the high comorbidity of Parkinson’s disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (SNCA), lysosomal enzyme β-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.
Item Description:Gesehen am 13.01.2025
Physical Description:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms25063219

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