TY - JOUR
T1 - Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions
AU - Shaharabani, Rona
AU - Ram-On, Maor
AU - Talmon, Yeshayahu
AU - Beck, Roy
N1 - Publisher Copyright: © 2018 National Academy of Sciences. All rights reserved.
PY - 2018/10/30
Y1 - 2018/10/30
N2 - 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.
AB - 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.
KW - Cryo-Tem
KW - Lamellar to hexagonal phase transition
KW - Multiple sclerosis
KW - Myelin
KW - SAXS
UR - http://www.scopus.com/inward/record.url?scp=85055621222&partnerID=8YFLogxK
U2 - 10.1073/pnas.1804275115
DO - 10.1073/pnas.1804275115
M3 - مقالة
C2 - 30322944
SN - 0027-8424
VL - 115
SP - 11156
EP - 11161
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 44
ER -