Lipid Investigation of Central and Peripheral Nervous System in Connatal Pelizaeus‐Merzbacher's Disease

Witer, Brigitte; Debuch, Hildegard; Klein, Harold P.

doi:10.1111/j.1471-4159.1980.tb09671.x

Cited by 22 publications

(5 citation statements)

References 36 publications

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“…Recent findings suggest that myelin instability in MSA is associated with a significant reduction in GalCer levels (Don et al, 2014 ). Similarly, both PMD, a leukodystrophy associated with mutations in proteolipid protein 1 (Trofatter et al, 1989 ), and Menkes disease, a lethal disorder of copper metabolism featuring neurodegeneration, hypotonia, weakness and spasticity, are also associated with significant reductions in myelin galactolipid levels (Lou et al, 1974 ; Witter et al, 1980 ). PMD is an unusual leukodystrophy because it results from the improper formation of myelin rather than from demyelination, the predominant cause of most leukodystrophies.…”

Section: Krabbe Disease Galactocerebrosidase and Galactosylceramidementioning

confidence: 99%

Lipid Involvement in Neurodegenerative Diseases of the Motor System: Insights from Lysosomal Storage Diseases

Dodge

2017

Front. Mol. Neurosci.

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Lysosomal storage diseases (LSDs) are a heterogeneous group of rare inherited metabolic diseases that are frequently triggered by the accumulation of lipids inside organelles of the endosomal-autophagic-lysosomal system (EALS). There is now a growing realization that disrupted lysosomal homeostasis (i.e., lysosomal cacostasis) also contributes to more common neurodegenerative disorders such as Parkinson disease (PD). Lipid deposition within the EALS may also participate in the pathogenesis of some additional neurodegenerative diseases of the motor system. Here, I will highlight the lipid abnormalities and clinical manifestations that are common to LSDs and several diseases of the motor system, including amyotrophic lateral sclerosis (ALS), atypical forms of spinal muscular atrophy, Charcot–Marie–Tooth disease (CMT), hereditary spastic paraplegia (HSP), multiple system atrophy (MSA), PD and spinocerebellar ataxia (SCA). Elucidating the underlying basis of intracellular lipid mislocalization as well as its consequences in each of these disorders will likely provide innovative targets for therapeutic research.

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Section: Krabbe Disease Galactocerebrosidase and Galactosylceramidementioning

confidence: 99%

Lipid Involvement in Neurodegenerative Diseases of the Motor System: Insights from Lysosomal Storage Diseases

Dodge

2017

Front. Mol. Neurosci.

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“…Together, cerebroside and cholesterol, which constitute -60 mol % of the lipid in myelin (or >80 mol % in the outer monolayer for the case of an asymmetric arrangement as discussed above), may be expected to increase impermeability, reduce water activity at the membrane surface, and reduce the ability of water and ions to move or to be transported across the myelin sheath (i.e., increase electrical resistance). Of particular relevance to these points is that in the dysmyelinating (leukodystrophic) disorder, Pelizaeus-Merzbacher's disease, in which there is aberrant nerve impulse conduction in peripheral nervous system neurons, cerebroside content is markedly reduced in the myelin sheath (40).…”

Section: Npgs-cholesterol-dipalmitoylphosphatidylcholine Bilayersmentioning

confidence: 99%

Interaction of cholesterol with galactocerebroside and galactocerebroside-phosphatidylcholine bilayer membranes

Ruocco¹,

Shipley²

1984

Biophysical Journal

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The interaction of the galactocerebroside, N-palmitoylgalactosylsphingosine (NPGS), with cholesterol has been studied by differential scanning calorimetry (DSC) and x-ray diffraction. Thermal and structural studies demonstrate complex behavior characterized by two endothermic transitions: transition I (TI approximately equal to 50-60 degrees C) corresponding to an NPGS-cholesterol bilayer gel----bilayer liquid crystal transition II (TII where TI less than TII less than TNPGS) corresponding to an NPGS bilayer crystal (stable E form)----bilayer liquid crystal transition. For mixtures containing from 6 to 80 mol % cholesterol, x-ray diffraction studies at 22 degrees C (T less than TI) indicate two separate lamellar phases; an NPGS crystal bilayer phase and a cholesterol monohydrate phase. For cholesterol concentrations less than 50 mol % at TI less than T less than TII, NPGS-cholesterol liquid crystal bilayer and excess NPGS crystal bilayer phases are observed. For greater than 50 mol % cholesterol concentrations at these temperatures, an excess cholesterol monohydrate phase coexists with the NPGS-cholesterol liquid crystal bilayers. At T greater than TII, complete NPGS-cholesterol miscibility is only observed for less than 50 mol % cholesterol concentrations, whereas at greater than 50 mol % cholesterol an excess cholesterol phase is present. The solid phase immiscibility of cerebroside and cholesterol at low temperatures is suggested to result from preferential NPGS-NPGS associations via hydrogen bonding. The unique thermal and structural behavior of NPGS-cholesterol dispersions is contrasted with the behavior of cholesterol-phosphatidycholine and cholesterol-sphingomyelin bilayers. Thermal and structural studies of NPGS in dipalmitoylphosphatidylcholine (DPPC)/cholesterol (1:1, molar ratio) bilayers have been performed. For dispersions containing less than 20 mol % NPGS at 22 degrees C there are no observable calorimetric transitions and x-ray diffraction studies indicate complete lipid miscibility. At greater than 20 mol % NPGS, a high temperature transition is observed that is shown by x-ray diffraction studies to be due to an excess NPGS crystal bilayer----liquid crystal bilayer transition. Complete miscibility of NPGS in DPPC/cholesterol bilayers is observed at T greater than TNPGS. The properties of NPGS/DPPC/cholesterol bilayers are discussed in terms of the lipid composition of the myelin sheath.

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“…Proper membrane function requires that these glycosphingolipids not only be present, but that their relative content be optimized. In fact, myelin function is impaired if GalCer content is too low, as is the case in Pelizaeius-Merzbacher's disease (Witter et al, 1980) or if GalCer content grossly exceeds optimum levels, as is the case in globoid cell leukodystrophy (e.g., Suzuki and Suzuki, 1989). Optimal GalCer content in myelin is also thought to be a key factor in the unusually low proton permeability of myelin lipid bilayers (Diaz and Monreal, 1994).…”

Section: Introductionmentioning

confidence: 99%

Macro-ripple phase formation in bilayers composed of galactosylceramide and phosphatidylcholine

Brown¹,

Anderson²,

Kulkarni³

1995

Biophysical Journal

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As determined by freeze fracture electron microscopy, increasing levels of bovine brain galactosylceramide (GalCer) altered the surface structure of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers by inducing a striking "macro-ripple" phase in the larger, multilamellar lipid vesicles at GalCer mole fractions between 0.4 and 0.8. The term "macro-ripple" phase was used to distinguish it from the P beta' ripple phase observed in saturated, symmetric-chain length phosphatidylcholines. Whereas the P beta' ripple phase displays two types of corrugations, one with a wavelength of 12-15 nm and the other with a wavelength of 25-35 nm, the macro-ripple phase occurring in GalCer/POPC dispersions was of one type with a wavelength of 100-110 nm. Also, in contrast to the extended linear arrays of adjacent ripples observed in the P beta' ripple phase, the macro-ripple phase of GalCer/POPC dispersions was interrupted frequently by packing defects resulting from double dislocations and various disclinations and, thus, appeared to be continuously twisting and turning. Control experiments verified that the macro-ripple phase was not an artifact of incomplete lipid mixing or demixing during preparation. Three different methods of lipid mixing were compared: a spray method of rapid solvent evaporation, a sublimation method of solvent removal, and solvent removal using a rotary evaporation apparatus. Control experiments also revealed that the macro-ripple phase was observed regardless of whether lipid specimens were prepared by either ultra-rapid or manual plunge freezing methods as well as either in the presence or absence of the cryo-protectant glycerol. The macro-ripple phase was always observed in mixtures that were fully annealed by incubation above the main thermal transition of both POPC and bovine brain GalCer before rapid freezing. If the GalCer mixed with POPC contained only nonhydroxy acyl chains or only 2-hydroxy acyl chains, then the occurrence of macro-ripple phase decreased dramatically.

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Lipid Investigation of Central and Peripheral Nervous System in Connatal Pelizaeus‐Merzbacher's Disease

Cited by 22 publications

References 36 publications

Lipid Involvement in Neurodegenerative Diseases of the Motor System: Insights from Lysosomal Storage Diseases

Lipid Involvement in Neurodegenerative Diseases of the Motor System: Insights from Lysosomal Storage Diseases

Interaction of cholesterol with galactocerebroside and galactocerebroside-phosphatidylcholine bilayer membranes

Macro-ripple phase formation in bilayers composed of galactosylceramide and phosphatidylcholine

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