Distinctive sphingolipid patterns in chronic multiple sclerosis lesions
Autor: | Ryszard Podemski, Małgorzata Bilińska, Robert K. Yu, Ewa Jaskiewicz, Wojciech Fortuna, Zdzislaw M. Szulc, Maria Podbielska, Toshio Ariga, Anna Pokryszko-Dragan, Ewa Kurowska, Edward L. Hogan |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Ceramide Pathology medicine.medical_specialty Multiple Sclerosis Central nervous system Inflammation QD415-436 030204 cardiovascular system & hematology Biochemistry White matter 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology medicine Humans brain lipids Research Articles ceramide 1-phosphate Aged mass spectrometry Aged 80 and over Sphingolipids ceramides business.industry Multiple sclerosis Neurodegeneration neurodegeneration Cell Biology Middle Aged central nervous system medicine.disease Sphingolipid 030104 developmental biology medicine.anatomical_structure chemistry inflammation Chronic Disease clinical lipidology lipidomics Biomarker (medicine) Female medicine.symptom business neurological diseases |
Zdroj: | Journal of Lipid Research, Vol 61, Iss 11, Pp 1464-1479 (2020) Journal of Lipid Research |
ISSN: | 0022-2275 |
Popis: | Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease. |
Databáze: | OpenAIRE |
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