Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions

Multiple sclerosis (MS) is an autoimmune disease, leading to the destruction of the myelin sheaths, the protective layers surrounding the axons. The etiology of the disease is unknown, although there are several postulated environmental factors that may contribute to it. Recently, myelin damage was...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-10, Vol.115 (44), p.11156-11161
Main Authors: Shaharabani, Rona, Ram-On, Maor, Talmon, Yeshayahu, Beck, Roy
Format: Article
Language:English
Subjects:
Axons
Biological Sciences
Cell Membrane - metabolism
Cell Membrane - pathology
Composition
Cytoplasm
Environment
Environmental changes
Environmental conditions
Environmental factors
Etiology
Hexagonal phase
Humans
Immune system
Lipid composition
Lipids
Lipids - physiology
Membranes
Multiple sclerosis
Multiple Sclerosis - metabolism
Multiple Sclerosis - pathology
Myelin
Myelin basic protein
Myelin Basic Protein - metabolism
Myelin Sheath - metabolism
Myelin Sheath - pathology
Phase transitions
Physical Sciences
Proteins
Sheaths
Stoichiometry
Structural damage
Transition points
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Summary:Multiple sclerosis (MS) is an autoimmune disease, leading to the destruction of the myelin sheaths, the protective layers surrounding the axons. The etiology of the disease is unknown, although there are several postulated environmental factors that may contribute to it. Recently, myelin damage was correlated to structural phase transition from a healthy stack of lamellas to a diseased inverted hexagonal phase as a result of the altered lipid stoichiometry and low myelin basic protein (MBP) content. In this work, we show that environmental conditions, such as buffer salinity and temperature, induce the same pathological phase transition as in the case of the lipid composition in the absence of MBP. These phase transitions have different transition points, which depend on the lipid’s compositions, and are ion specific. In extreme environmental conditions, we find an additional dense lamellar phase and that the native lipid composition results in similar pathology as the diseased composition. These findings demonstrate that several local environmental changes can trigger pathological structural changes. We postulate that these structural modifications result in myelin membrane vulnerability to the immune system attacks and thus can help explain MS etiology.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1804275115