High cholesterol level is essential for myelin membrane growth

@article{Saher2005HighCL,
  title={High cholesterol level is essential for myelin membrane growth},
  author={Gesine Saher and Britta Br{\"u}gger and Corinna Lappe-Siefke and Wiebke M{\"o}bius and Ryuichi Tozawa and Michael C Wehr and Felix T. Wieland and Shun Ishibashi and Klaus-Armin Nave},
  journal={Nature Neuroscience},
  year={2005},
  volume={8},
  pages={468-475}
}
Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months… Expand
Cholesterol in myelin biogenesis and hypomyelinating disorders.
TLDR
This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. Expand
Cholesterol: A Novel Regulatory Role in Myelin Formation
TLDR
The role of cholesterol is summarized in myelin biogenesis and myelin disease, where cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Expand
Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice
Astrocyte-derived cholesterol supports brain cells under physiological conditions. However, in demyelinating lesions, astrocytes downregulate cholesterol synthesis and the cholesterol that isExpand
Survival of adult neurons lacking cholesterol synthesis in vivo
TLDR
It is concluded that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Expand
Metabolism and functions of lipids in myelin.
TLDR
It is postulate that change in myelin lipid composition might be relevant for the understanding of aging and demyelinating diseases and in supporting long-term maintenance of myelin. Expand
CHAPTER 4 CNS myelination is dependent on astrocyte lipid metabolism
Myelination requires massive incorporation of lipids into the expanding glial cell membrane, yielding these cells very active in lipid metabolism. Whether myelin membrane formation fully relies onExpand
Lipids in regulating oligodendrocyte structure and function.
  • L. Montani
  • Medicine, Biology
  • Seminars in cell & developmental biology
  • 2020
TLDR
Key findings in the role of Lipids in CNS Cell Physiology and Pathology are summarized, while presenting the main related human diseases. Expand
Cholesterol Regulates the Endoplasmic Reticulum Exit of the Major Membrane Protein P0 Required for Peripheral Myelin Compaction
TLDR
In vitro and in vivo evidence is provided that high-level cholesterol coordinates P0 export with myelin membrane synthesis, which is required for the correct stoichiometry of myelin components and for myelin compaction. Expand
A critical role for the cholesterol‐associated proteolipids PLP and M6B in myelination of the central nervous system
TLDR
A critical role for proteolipids in cholesterol accumulation is demonstrated in the formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. Expand
Npc1 Acting in Neurons and Glia Is Essential for the Formation and Maintenance of CNS Myelin
TLDR
It is demonstrated that lipid uptake and intracellular transport by neurons and oligodendrocytes through an Npc1-dependent pathway is required for both the formation and maintenance of CNS myelin. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 56 REFERENCES
Brain Cholesterol: Long Secret Life Behind a Barrier
TLDR
There is a highly efficient apolipoprotein-dependent recycling of cholesterol in the brain, with minimal losses to the circulation. Expand
Membrane traffic in myelinating oligodendrocytes
TLDR
This review summarises what is currently known about myelin protein trafficking and mistrafficking in oligodendrocytes and presents data demonstrating distinct transport pathways for myelin structural proteins and the expression of SNARE proteins in differentiating oligodends. Expand
Normal metabolism but different physical properties of myelin from mice deficient in proteolipid protein
TLDR
It is concluded that PLPnull myelin is physically less stable and/or less dense than wt myelin and should be preferentially found in these “slower‐sedimenting” myelin precursor fragments. Expand
Myelin glycolipids and their functions
TLDR
An approach for unravelling the roles played by various lipids in the myelin membrane involves knocking out the genes encoding important enzymes in lipid biosynthesis, and the recent ablation of the ceramide galactosyltransferase gene in mice is the first example. Expand
Galactolipids are molecular determinants of myelin development and axo-glial organization.
TLDR
By interbreeding the CGT mutants with mice that lack myelin-associated glycoprotein, it has been shown that these specialized myelin lipids and proteins act in concert to promote axo-glial adhesion during myelinogenesis. Expand
Assembly of Myelin by Association of Proteolipid Protein with Cholesterol- and Galactosylceramide-Rich Membrane Domains
TLDR
Proteolipid protein (PLP), the major myelin protein, was recovered from cultured oligodendrocytes from a low-density CHAPS-insoluble membrane fraction (CIMF) enriched in myelin lipids and was supported by the finding that it was efficiently cross-linked to photoactivable cholesterol, but not to phosphatidylcholine, which is underrepresented in both myelin and CIMF. Expand
Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination
TLDR
It is shown that Cnp1, which encodes 2′,3′-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly, and the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Expand
Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes?
  • F. Pfrieger
  • Biology, Medicine
  • BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2003
TLDR
A new kind of job-sharing between neurons and astrocytes is proposed to improve the still insufficient understanding of brain cholesterol metabolism and its role in neurodegeneration. Expand
Origin of cholesterol in myelin
TLDR
Almost all cholesterol accumulating in brain during development is locally synthesized, which shows that incorporation of radioactive precursors into brain cholesterol is roughly proportional to the rate of myelination and that, once incorporated, radioactive cholesterol is relatively stable metabolically. Expand
Myelin deficient mice: Expression of myelin basic protein and generation of mice with varying levels of myelin
TLDR
It is demonstrated in mld mice that the gene encoding myelin basic protein (MBP) is expressed at decreased levels and on an abnormal temporal schedule relative to the wild-type gene. Expand
...
1
2
3
4
5
...