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

• Published in: iScience
• Main Authors: Tatiane Piedade de Souza, Gilderlanio Santana de Araújo, Leandro Magalhães, Giovanna C. Cavalcante, Arthur Ribeiro-dos-Santos, Camille Sena-dos-Santos, Caio Santos Silva, Gracivane Lopes Eufraseo, Alana de Freitas Escudeiro, Giordano Bruno Soares-Souza, Bruno Lopes Santos-Lobato, Ândrea Ribeiro-dos-Santos
• Format: Article
• Language: English
• Published: Elsevier 2024-09-01
• Subjects: Clinical genetics; Molecular neuroscience; Clinical neuroscience
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004224020601
• ISSN: 2589-0042

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.