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Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
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Distinctive sphingolipid patterns in chronic multiple sclerosis lesions.

Maria Podbielska1,2, Zdzislaw M Szulc1, Toshio Ariga3

  • 1Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.

Journal of Lipid Research
|August 10, 2020
PubMed
Summary
This summary is machine-generated.

Sphingolipid profiles differ between active and inactive multiple sclerosis (MS) lesions. Ceramide 1-phosphate (C1P) may serve as a biomarker for the progressive phase of MS, aiding future treatment strategies.

Keywords:
brain lipidscentral nervous systemceramide 1-phosphateceramidesclinical lipidologyinflammationlipidomicsmass spectrometryneurodegenerationneurological diseases

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Area of Science:

  • Neuroimmunology
  • Neurodegenerative Diseases
  • Biochemistry

Background:

  • Multiple sclerosis (MS) involves immune-mediated demyelination and axonal loss in the central nervous system (CNS).
  • MS pathology presents active and inactive/progressive phases, necessitating biomarkers for understanding mechanisms and predicting disease course.
  • Current research seeks reliable biomarkers to identify MS pathomechanisms and forecast its clinical progression.

Purpose of the Study:

  • To identify specific sphingolipid (SL) species as potential biomarkers for inflammatory and neurodegenerative processes in MS.
  • To investigate sphingolipidomic profiles in different MS lesion types and compare them to normal CNS tissue.

Main Methods:

  • Sphingolipidomic analysis using High-Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC-MS/MS).
  • Analysis of post-mortem CNS specimens, including normal-appearing white matter (NAWM) from normal CNS (nCNS) and chronic MS lesions (active and inactive).

Main Results:

  • Distinctive sphingolipid modification patterns were observed in chronic inactive MS (In-MS) lesions compared to nCNS NAWM and active MS (Ac-MS) lesions.
  • In-MS lesions showed decreased dihydroceramide (dhCer), ceramide (Cer), and sphingomyelin (SM) subspecies, with increased hexosylceramide and ceramide 1-phosphate (C1P) subspecies.
  • Ac-MS lesions exhibited a significant increase in major dhCer subspecies compared to nCNS NAWM.

Conclusions:

  • The findings suggest distinct sphingolipid metabolic pathways operate in active versus inactive phases of progressive MS.
  • Ceramide 1-phosphate (C1P) emerges as a potential novel biomarker for the inactive/progressive phase of MS.
  • Identification of C1P may facilitate the development of future prognostic and therapeutic strategies for multiple sclerosis.