Unveiling differential gene co-expression networks and its effects on levodopa-induced dyskinesia

Levodopa-induced dyskinesia (LID) refers to involuntary motor movements of chronic use of levodopa in Parkinson’s disease (PD) that negatively impact the overall well-being of people with this disease. The molecular mechanisms involved in LID were investigated through whole-blood transcriptomic anal...

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Published in:iScience 2024-09, Vol.27 (9), p.110835, Article 110835
Main Authors: Piedade de Souza, Tatiane, Santana de Araújo, Gilderlanio, Magalhães, Leandro, Cavalcante, Giovanna C., Ribeiro-dos-Santos, Arthur, Sena-dos-Santos, Camille, Silva, Caio Santos, Eufraseo, Gracivane Lopes, de Freitas Escudeiro, Alana, Soares-Souza, Giordano Bruno, Santos-Lobato, Bruno Lopes, Ribeiro-dos-Santos, Ândrea
Format: Article
Language:English
Subjects:
Clinical genetics
Clinical neuroscience
Molecular neuroscience
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Summary:Levodopa-induced dyskinesia (LID) refers to involuntary motor movements of chronic use of levodopa in Parkinson’s disease (PD) that negatively impact the overall well-being of people with this disease. The molecular mechanisms involved in LID were investigated through whole-blood transcriptomic analysis for differential gene expression and identification of new co-expression and differential co-expression networks. We found six differentially expressed genes in patients with LID, and 13 in patients without LID. We also identified 12 co-expressed genes exclusive to LID, and six exclusive hub genes involved in 23 gene-gene interactions in patients with LID. Convergently, we identified novel genes associated with PD and LID that play roles in mitochondrial dysfunction, dysregulation of lipid metabolism, and neuroinflammation. We observed significant changes in disease progression, consistent with previous findings of maladaptive plastic changes in the basal ganglia leading to the development of LID, including a chronic pro-inflammatory state in the brain. [Display omitted] •Differential expression analysis revealed ten new transcripts altered in PD patients•Dyskinesia patients showed an exclusive gene co-expression network•Alterations in mitochondrial genes may contribute to the pro-inflammatory state in PD•Inflammatory pathways may contribute to the onset of levodopa-induced dyskinesia Clinical genetics; Molecular neuroscience; Clinical neuroscience
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.110835