Multiomics approach identifies dysregulated lipidomic and proteomic networks in Parkinson’s disease patients mutated in TMEM175

• Published in: NPJ Parkinson's Disease 2025-01, Vol.11 (1), p.23-24, Article 23
• Main Authors: Carrillo, Federica, Ghirimoldi, Marco, Fortunato, Giorgio, Palomba, Nicole Piera, Ianiro, Laura, De Giorgis, Veronica, Khoso, Shahzaib, Giloni, Tiziana, Pietracupa, Sara, Modugno, Nicola, Barberis, Elettra, Manfredi, Marcello, Esposito, Teresa
• Format: Article
• Language: English
• Subjects: 631/378/1689/1718; 692/53/2423; Autophagy; Biomedical and Life Sciences; Biomedicine; Fibroblasts; Metabolism; Mutation; Neurology; Neurosciences; Proteins
• ISSN: 2373-8057; 2373-8057
• DOI: 10.1038/s41531-024-00853-5

Parkinson’s disease (PD) represents one of the most frequent neurodegenerative disorders for which clinically useful biomarkers remain to be identified and validated. Here, we adopted an untargeted omics approach to disclose lipidomic, metabolomic and proteomic alterations in plasma and in dermal fibroblasts of PD patients carrying mutations in TMEM175 gene. We revealed a wide dysregulation of lysosome, autophagy, and mitochondrial pathways in these patients, supporting a role of this channel in regulating these cellular processes. The most significant altered lipid classes were Fatty acyls, Glycerophospholipids and Phosphosphingolipids. The plasma level of Phosphatidylcholines (PC) and Phosphatidylinositol (PI) 34:1 significantly correlated with an earlier age at onset of the disease in TMEM175 patients ( p  = 0.008; p  = 0.006). In plasma we also observed altered amino acids metabolic pathways in PD patients. We highlighted that increased level of L-glutamate strongly correlated ( p