Nature sub-journal interpretation! Cholesterol recycling may help support myelin repair!

December 29, 2020 // -- It is well known that cholesterol deposition in blood vessels is harmful in diseases such as atherosclerosis, and similar problems occur in neurological diseases such as multiple sclerosis, in which cholesterol-rich myelin defects occur during regeneration, and the normal function of devouring cells to recover cholesterol from defective myelin is impaired, which in turn leads to the production of foam cells, which can actually suffocate cholesterol.
so far, researchers don't know exactly what mechanism blocks the re-absorption of cholesterol by phagocytos.
a recent study published in the international journal Nature Neuroscience entitled "Microglia easy repair of the demyelinated lesions via post-squalene sterol synthesis", scientists from the Max Planck Institute and other institutions through the study The synthesis of cholesterol in phagocytosis plays an important role in this circulatory process, and the pharmacological support for cholesterol synthesis may improve the regeneration of lesions in the brain in mice, and studies have found that it may help scientists change the treatment of myelin-based diseases such as multiple sclerosis.
Photo Source: MPI for Analm Medicine/Depp, Berghoff like a string of beads, cholesterol- and lipid-rich myelin covers nerve fibers and remains insulated on them, isolating and effectively transmitting impulses.
We all know that a bunch of beads breaks, but only if they can't be reused, damage the vacuum cleaner, and stay permanently on the floor.
this is common in chronic brain lesions, where myelin disappears permanently, while small glial cells closely related to macrophages are scavenger cells in the brain, like the vacuum cleaners mentioned above.
In a person's lifetime, a single myelin is replaced, and during normal regeneration, scavenger cells ingest cholesterol and other lipids from the defective myelin so that they can be recycled and used to repair tissue, an efficient repair mechanism that may continue to occur in healthy individuals.
The synthesis of cholesterol supports the recycling of cholesterol, researcher Saher and colleagues investigated the key role of cholesterol and other lipids in the body's nervous system in physiological and pathological conditions, and by conducting a joint study, the researchers investigated how multiple cell types in the brain treat cholesterol during myelin regeneration.
The researchers used genes to knock out the cholesterol synthesis process in a cell type in the brains of mice, and then studied the effects of this process on myelin regeneration in the brains of mice, and found that mutant mice with cholesterol synthesis defects in scavenger cells in the brain behaved in a way that surprised scientists that they could still absorb cholesterol from degraded myelin but could not recover it.
And because many small glial cells can be converted into foam cells and eventually die from eating too much cholesterol, myelin's ability to regenerate is significantly reduced, so researchers wanted to know why phagocytoids block the production of re-used cholesterol.
researchers say a cholesterol synthesis intermediate called desmosterol is particularly important for the degradation and reconstruction of myelin membranes from degradation to regeneration, as a signaling molecule that not only causes cholesterol to mobilize to form a new myelin, but also helps to create a regenerative environment.
by using the early intermediate of cholesterol synthesis, squalene, can support the cholesterol synthesis process rationally, thus promoting the endogenous circulation of myelin.
In this study, researchers studied mice to reveal that terpene or can be used as a new potential factor in therapy to help treat myelin diseases such as multiple sclerosis;
() References: Berghoff, S.A., Spieth, L., Sun, T. et al. Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis. Nat Neurosci 24, 47–60 (2021). doi:10.1038/s41593-020-00757-6【2】Cholesterol recycling supports myelin repairby Max Planck Society。