Objective: To investigate the landscape of sphingolipid metabolism gene expression in Parkinson’s disease (PD).To investigate the landscape of sphingolipid metabolism gene expression in Parkinson’s disease (PD).

Background: PD is the fast growing neurodegenerative disorder worldwide, characterized by Lewy body formation and dopaminergic neuron loss. Lipid dyshomeostasis is increasingly recognized as a critical hub of PD pathogenesis, supported by genetic and lipidomic evidence. Sphingolipids are the commonly dysregulated lipid species in PD. However, the landscape of sphingolipid metabolism enzyme changes in PD is largely unknown.

Method: We leveraged 18 datasets of human postmortem substantia nigra from Gene Expression Omnibus (GEO) and performed meta-analysis to compare the mRNA expression levels of targeted genes involved in sphingolipid metabolism  between PD patients (N=140) and non-disease controls (N=166).

Results: Among the 79 sphingolipid metabolism genes, 15 genes were upregulated and 19 genes were downregulated. Genes involved in ceramide de novo synthesis were upregulated, which are in line with GBA1 loss-of-function mutations are the most genetic risk factor for PD. Those involved in glycosphingolipid and acylceramide metabolism were downregulated.

Conclusion: These results will provide further insights into lipid dysregulation, particularly sphingolipid metabolism, in the pathophysiology of PD and may facilitate the identification of novel biomarkers and therapeutic targets.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-sphingolipid-metabolism-gene-expression-in-the-parkinsons-disease-postmortem-brain-dataset/