Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study
Abstract Introduction Sleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, whi...
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2023-09-01
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| Series: | Neurology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40120-023-00542-0 |
| _version_ | 1797629876442759168 |
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| author | Yongang Li GuiKai Ji Mengjia Lian Xuan Liu Ying Xu Yaxing Gui |
| author_facet | Yongang Li GuiKai Ji Mengjia Lian Xuan Liu Ying Xu Yaxing Gui |
| author_sort | Yongang Li |
| collection | DOAJ |
| description | Abstract Introduction Sleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, which in turn contributes to different types of sleep disorders. Methods We used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations. Results PLA2G6 mutations (c.1966C > G, Leu656Val; c.2077C > G, Leu693Val; c.1791delC, His597fx69) significantly increase the exosomal content of glycerophospholipids and lysophospholipids, specifically phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Exosome surface presence of melatomin receptor 1A (MTNR1A) was detectable only in patients with PLA2G6 mutations. We have further shown that, in patients with PD carrying PLA2G6 mutations, sleep latency was significantly longer compared to those carrying WT PLA2G6, and we speculate that functional PLA2G6 mutations lead to structural changes and lipid deregulation of exosomes, which in turn alters exosomal cargo and affects PD-related sleep disorders. In SMPD1, G508R variant-carrying patients with PD abundance of sphingomyelins was significantly higher and had significantly shorter rapid eye movement sleep. Conclusions Our study demonstrated that the disturbed composition and function of CSF-derived exosome lipidome during the pathological stage of PD may affect different types of sleep disorder in PD. |
| first_indexed | 2024-03-11T10:59:57Z |
| format | Article |
| id | doaj.art-320512bc938943eda5af202a16194ce1 |
| institution | Directory Open Access Journal |
| issn | 2193-8253 2193-6536 |
| language | English |
| last_indexed | 2024-03-11T10:59:57Z |
| publishDate | 2023-09-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Neurology and Therapy |
| spelling | doaj.art-320512bc938943eda5af202a16194ce12023-11-12T12:34:07ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362023-09-011262021204010.1007/s40120-023-00542-0Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics StudyYongang Li0GuiKai Ji1Mengjia Lian2Xuan Liu3Ying Xu4Yaxing Gui5Department of Neurology, The First People’s Hospital of WenlingShanghai FuXing Senior High SchoolDepartment of Neurology, The First People’s Hospital of WenlingDepartment of Neurology, The First People’s Hospital of WenlingDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineAbstract Introduction Sleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, which in turn contributes to different types of sleep disorders. Methods We used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations. Results PLA2G6 mutations (c.1966C > G, Leu656Val; c.2077C > G, Leu693Val; c.1791delC, His597fx69) significantly increase the exosomal content of glycerophospholipids and lysophospholipids, specifically phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Exosome surface presence of melatomin receptor 1A (MTNR1A) was detectable only in patients with PLA2G6 mutations. We have further shown that, in patients with PD carrying PLA2G6 mutations, sleep latency was significantly longer compared to those carrying WT PLA2G6, and we speculate that functional PLA2G6 mutations lead to structural changes and lipid deregulation of exosomes, which in turn alters exosomal cargo and affects PD-related sleep disorders. In SMPD1, G508R variant-carrying patients with PD abundance of sphingomyelins was significantly higher and had significantly shorter rapid eye movement sleep. Conclusions Our study demonstrated that the disturbed composition and function of CSF-derived exosome lipidome during the pathological stage of PD may affect different types of sleep disorder in PD.https://doi.org/10.1007/s40120-023-00542-0Parkinson's diseaseExosomesLipidsPLA2G6SMPD1 |
| spellingShingle | Yongang Li GuiKai Ji Mengjia Lian Xuan Liu Ying Xu Yaxing Gui Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study Neurology and Therapy Parkinson's disease Exosomes Lipids PLA2G6 SMPD1 |
| title | Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study |
| title_full | Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study |
| title_fullStr | Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study |
| title_full_unstemmed | Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study |
| title_short | Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study |
| title_sort | effect of pla2g6 and smpd1 variants on the lipid metabolism in the cerebrospinal fluid of patients with parkinson s disease a non targeted lipidomics study |
| topic | Parkinson's disease Exosomes Lipids PLA2G6 SMPD1 |
| url | https://doi.org/10.1007/s40120-023-00542-0 |
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