Integrated Metabolomics and Proteomics Analysis Reveals Plasma Lipid Metabolic Disturbance in Patients With Parkinson’s Disease

Abstract

Parkinson's disease (PD) is a common neurodegenerative disease in the elderly with a pathogenesis that remains unclear. We aimed to explore its pathogenesis through plasma integrated metabolomics and proteomics analysis. The clinical data of consecutively recruited PD patients and healthy controls were assessed. Fasting plasma samples were obtained and analyzed using metabolomics and proteomics methods. After that, differentially expressed metabolites and proteins were identified for further bioinformatics analysis. No significant difference was found in the clinical data between these two groups. Eighty-three metabolites were differentially expressed in PD patients identified by metabolomics analysis. These metabolites were predominately lipid and lipid-like molecules (63%), among which 25% were sphingolipids. The sphingolipid metabolism pathway was enriched and tended to be activated in the following KEGG pathway analysis. According to the proteomics analysis, forty proteins were identified to be differentially expressed, seven of which were apolipoproteins. Furthermore, five of the six top ranking Gene Ontology terms from cellular components and eleven of the other fourteen Gene Ontology terms from biological processes were directly associated with lipid metabolism. In KEGG pathway analysis, the five enriched pathways were also significantly related with lipid metabolism (p < 0.05). Overall, Parkinson's disease is associated with plasma lipid metabolic disturbance, including an activated sphingolipid metabolism and decreased apolipoproteins.

Advancing Personalized Medicine in Common Forms of Parkinson’s Disease through Genetics: Current Therapeutics and the Future of Individualized Management

“…This unbiased and data-driven study provided a foundational resource for the PD community through a publicly available pathways browser. Pathways previously implicated by genetics and functional studies also found to be significant in this study include endocytic trafficking [ 61 , 62 ], autophagic-lysosomal function [ 51 , 63 ], mitochondrial function [ 64 , 65 ], protein aggregation [ 66 ], neuronal transmission [ 67 ], lipid metabolism [ 68 , 69 ], and certain inflammatory pathways [ 70 , 71 ] ( Figure 1 ). It has also been shown that similar pathways can be deficient in both familial and common forms of PD [ 51 , 62 ] and multiple networks can overlap or a single pathway can act alone.…”

Sphingomyelin and Medullary Sponge Kidney Disease: A Biological Link Identified by Omics Approach

“…At our knowledge, this is the first report describing a specific metabolic fingerprint of MSK and the possible involvement of sphingomyelin in the MSK-associated biological impairment. Instead, alterations in the metabolism of sphingomyelin and other sphingolipids have been extensively reported in other diseases including neurodegenerative [Alzheimer's disease ( 31 ), Parkinson's ( 32 ), multiple sclerosis ( 33 ), Lewy body dementia ( 34 )], vascular ( 35 ), and bone disorders ( 30 ).…”

Dopaminergic System Alteration in Anxiety and Compulsive Disorders: A Systematic Review of Neuroimaging Studies

“…Serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors are usually used as part of the preferred initial treatment (Katzman et al, 2014 ) with response rates in the range of 30–50% (Reinhold and Rickels, 2015 ). We have performed a number of studies about this issue before (Dong et al, 2017a , b ; Dong et al, 2018a ; Chen et al, 2020 ; Hu et al, 2020 ). The main aim of this study was to assess whether dopaminergic dysregulation can be detected in anxiety and obsessive disorder with any degree of consistency and specificity.…”