desmosterol has been researched along with Multiple-Sclerosis* in 2 studies
2 other study(ies) available for desmosterol and Multiple-Sclerosis
| Article | Year |
|---|---|
Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis.
The repair of inflamed, demyelinated lesions as in multiple sclerosis (MS) necessitates the clearance of cholesterol-rich myelin debris by microglia/macrophages and the switch from a pro-inflammatory to an anti-inflammatory lesion environment. Subsequently, oligodendrocytes increase cholesterol levels as a prerequisite for synthesizing new myelin membranes. We hypothesized that lesion resolution is regulated by the fate of cholesterol from damaged myelin and oligodendroglial sterol synthesis. By integrating gene expression profiling, genetics and comprehensive phenotyping, we found that, paradoxically, sterol synthesis in myelin-phagocytosing microglia/macrophages determines the repair of acutely demyelinated lesions. Rather than producing cholesterol, microglia/macrophages synthesized desmosterol, the immediate cholesterol precursor. Desmosterol activated liver X receptor (LXR) signaling to resolve inflammation, creating a permissive environment for oligodendrocyte differentiation. Moreover, LXR target gene products facilitated the efflux of lipid and cholesterol from lipid-laden microglia/macrophages to support remyelination by oligodendrocytes. Consequently, pharmacological stimulation of sterol synthesis boosted the repair of demyelinated lesions, suggesting novel therapeutic strategies for myelin repair in MS. Topics: Animals; Cholesterol; Demyelinating Diseases; Desmosterol; Encephalomyelitis, Autoimmune, Experimental; Female; Gene Expression Profiling; Humans; Inflammation; Lipid Metabolism; Liver X Receptors; Mice; Mice, Inbred C57BL; Microglia; Middle Aged; Multiple Sclerosis; Oligodendroglia; Phagocytosis; Squalene; Sterols | 2021 |
Steryl esters and their relationship to normal and diseased human central nervous system.
The composition and distribution of steryl esters in human diseased or developing brain tissue has been studied. The abnormal brain conditions included sudanophilic leukodystrophy, multiple sclerosis plaque, subacute sclerosing panencephalitis, and an old cerebral infarction and two types of brain-derived tumors. In addition to the above abnormal tissue, steryl esters were also examined in developing and normal adult human brain. It was found upon subcellular fractionation that the steryl ester was localized mainly in the soluble nonparticulate material. A cholesteryl ester-rich fraction, floating on top of distilled water after centrifugation, was recovered only in the developing brain or in instances where there was myelin damage. The sterol portion of the steryl ester was largely cholesterol. The fatty acid moiety was mainly composed of C(16), C(18), and C(20) fatty acids. The dominant fatty acid was oleic acid, and the proportion of this fatty acid increased in demyelination. Although there were great differences in the quantities of steryl ester found, the fatty acid profiles of normal developing and adult brain were quite similar. As has been noted by others, the fatty acid composition of brain steryl esters most closely resembles that of brain phosphatidylcholine. Topics: Adult; Brain; Brain Neoplasms; Cholesterol; Chromatography; Chromatography, Gas; Corpus Callosum; Desmosterol; Esters; Fatty Acids; Humans; Infant; Infant, Newborn; Infarction; Lanosterol; Leukodystrophy, Metachromatic; Multiple Sclerosis; Neurilemmoma; Oligodendroglioma; Silicon Dioxide; Sterols; Subacute Sclerosing Panencephalitis; Subcellular Fractions | 1974 |