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

Shaharabani, Rona; Ram-On, Maor; Talmon, Yeshayahu; Beck, Roy

doi:10.1073/pnas.1804275115

Cited by 23 publications

(29 citation statements)

References 63 publications

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“…In the recent years particularly complex biomimetic membrane systems mimicking the myelin membrane have come into the focus of science (e.g. [11][12][13][14][15][16][17]. In those biomimetic systems, it is the complex lipid composition and the asymmetry of the lipid distribution between inner and outer membrane leaflets of myelin membranes that are considered.…”

mentioning

confidence: 99%

Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis

Krugmann

Rădulescu

Appavou

et al. 2020

Sci Rep

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Myelin basic protein (MBP) and its interaction with lipids of the myelin sheath plays an important part in the pathology of multiple sclerosis (MS). Previous studies observed that changes in the myelin lipid composition lead to instabilities and enhanced local curvature of MBP-lipid multilayer structures. We investigated the molecular origin of the instability and found that the diseased lipid membrane has a 25% lower bending rigidity, thus destabilizing smooth $$>1\,$$ > 1 µm curvature radius structures such as in giant unilamellar vesicles. MBP-mediated assembling of lipid bilayers proceeds in two steps, with a slow second step occurring over many days where native lipid membranes assemble into well-defined multilayer structures, whereas diseased lipid membranes form folded assemblies with high local curvature. For both native and diseased lipid mixtures we find that MBP forms dense liquid phases on top of the lipid membranes mediating attractive membrane interactions. Furthermore, we observe MBP to insert into its bilayer leaflet side in case of the diseased lipid mixture, whereas there is no insertion for the native mixture. Insertion increases the local membrane curvature, and could be caused by a decrease of the sphingomyelin content of the diseased lipid mixture. These findings can help to open a pathway to remyelination strategies.

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mentioning

confidence: 99%

Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis

Krugmann

Rădulescu

Appavou

et al. 2020

Sci Rep

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“…Ca 2+ is a major divalent cation in myelin and has numerous roles in oligodendrocyte differentiation and myelination [128,[248][249][250][251][252]. Ca 2+ has been shown to affect the production of MBP [253], and more notably, its membrane binding [53,90,247]. On the other hand, MBP affects the amount of Ca 2+ in oligodendrocytes [72,254].…”

Section: Basic Proteins and Multiple Sclerosismentioning

confidence: 99%

“…In addition, the proteolytic susceptibility of deiminated MBP is higher [229,242]. In MS, the lipid composition and ion content of myelin are altered, affecting the membranestacking activity of MBP [246,247]. Ca 2+ is a major divalent cation in myelin and has numerous roles in oligodendrocyte differentiation and myelination [128,[248][249][250][251][252].…”

Section: Basic Proteins and Multiple Sclerosismentioning

confidence: 99%

Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease

Raasakka

Kursula

2020

Cells

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Myelin ensheathes selected axonal segments within the nervous system, resulting primarily in nerve impulse acceleration, as well as mechanical and trophic support for neurons. In the central and peripheral nervous systems, various proteins that contribute to the formation and stability of myelin are present, which also harbor pathophysiological roles in myelin disease. Many myelin proteins have common attributes, including small size, hydrophobic segments, multifunctionality, longevity, and regions of intrinsic disorder. With recent advances in protein biophysical characterization and bioinformatics, it has become evident that intrinsically disordered proteins (IDPs) are abundant in myelin, and their flexible nature enables multifunctionality. Here, we review known myelin IDPs, their conservation, molecular characteristics and functions, and their disease relevance, along with open questions and speculations. We place emphasis on classifying the molecular details of IDPs in myelin, and we correlate these with their various functions, including susceptibility to post-translational modifications, function in protein–protein and protein–membrane interactions, as well as their role as extended entropic chains. We discuss how myelin pathology can relate to IDPs and which molecular factors are potentially involved.

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“…In MS, the lipid composition and ion content of myelin are altered, affecting the membranestacking activity of MBP [241,242]. Ca 2+ is a major divalent cation in myelin and has numerous roles in oligodendrocyte differentiation and myelination [125,[243][244][245][246][247].…”

Section: Basic Proteins and Multiple Sclerosismentioning

confidence: 99%

“…Ca 2+ is a major divalent cation in myelin and has numerous roles in oligodendrocyte differentiation and myelination [125,[243][244][245][246][247]. Ca 2+ has been shown to affect the production of MBP [248], and more notably, its membrane binding [53,90,242]. On the other hand, MBP affects the amount of Ca 2+ in oligodendrocytes [72,249].…”

Section: Basic Proteins and Multiple Sclerosismentioning

confidence: 99%

Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease

Raasakka

Kursula

2020

Preprint

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Myelin ensheathes selected axonal segments within the nervous system, resulting primarily in nerve impulse acceleration, as well as mechanical and trophic support for neurons. In the central and peripheral nervous systems, various proteins that contribute to the formation and stability of myelin are present, which also harbour pathophysiological roles in myelin disease. Many myelin proteins share common attributes, including small size, high hydrophobicity, multifunctionality, longevity, and intrinsic disorder. With recent advances in protein biophysical characterization and bioinformatics, it has become evident that intrinsically disordered proteins (IDPs) are abundant in myelin, and their flexible nature enables multifunctionality. Here, we review known myelin IDPs, their conservation, molecular characteristics and functions, and their disease relevance, along with open questions and speculations. We place emphasis on classifying the molecular details of IDPs in myelin and correlate these with their various functions, including susceptibility to post-translational modifications, function in protein-protein and protein-membrane interactions, as well as their role as extended entropic chains. We discuss how myelin pathology can relate to IDPs and which molecular factors are potentially involved.

show abstract

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

Cited by 23 publications

References 63 publications

Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis

Membrane stiffness and myelin basic protein binding strength as molecular origin of multiple sclerosis

Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease

Flexible Players within the Sheaths: The Intrinsically Disordered Proteins of Myelin in Health and Disease

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