New Compound Promotes Healing of Myelin in Nervous System Disorders

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seeva
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New Compound Promotes Healing of Myelin in Nervous System Disorders

Post by seeva » Mon Sep 09, 2019 1:21 am

HI FRIENDS PLEASE READ
https://medicalxpress.com/news/2019-09- ... rders.html
regards
seeva

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NHE
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Re: New Compound Promotes Healing of Myelin in Nervous System Disorders

Post by NHE » Mon Sep 09, 2019 2:26 am

A modified flavonoid accelerates oligodendrocyte maturation and functional remyelination
https://onlinelibrary.wiley.com/doi/abs ... glia.23715
  • Myelination delay and remyelination failure following insults to the central nervous system (CNS) impede axonal conduction and lead to motor, sensory and cognitive impairments. Both myelination and remyelination are often inhibited or delayed due to the failure of oligodendrocyte progenitor cells (OPCs) to mature into myelinating oligodendrocytes (OLs). Digestion products of the glycosaminoglycan hyaluronan (HA) have been implicated in blocking OPC maturation, but how these digestion products are generated is unclear. We tested the possibility that hyaluronidase activity is directly linked to the inhibition of OPC maturation by developing a novel modified flavonoid that functions as a hyaluronidase inhibitor. This compound, called S3, blocks some but not all hyaluronidases and only inhibits matrix metalloproteinase activity at high concentrations. We find that S3 reverses HA‐mediated inhibition of OPC maturation in vitro, an effect that can be overcome by excess recombinant hyaluronidase. Furthermore, we find that hyaluronidase inhibition by S3 accelerates OPC maturation in an in vitro model of perinatal white matter injury. Finally, blocking hyaluronidase activity with S3 promotes functional remyelination in mice with lysolecithin‐induced demyelinating corpus callosum lesions. All together, these findings support the notion that hyaluronidase activity originating from OPCs in CNS lesions is sufficient to prevent OPC maturation, which delays myelination or blocks remyelination. These data also indicate that modified flavonoids can act as selective inhibitors of hyaluronidase activity and can promote OPC maturation, making them excellent candidates to accelerate myelination or promote remyelination following perinatal and adult CNS insults.

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Re: New Compound Promotes Healing of Myelin in Nervous System Disorders

Post by NHE » Mon Sep 09, 2019 2:42 am

From 2003...

Flavonoids inhibit myelin phagocytosis by macrophages; a structure–activity
relationship study

Biochemical Pharmacology. 2003 Mar 1;65(5):877-85.
  • Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease. Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds, are able to influence myelin phagocytosis by macrophages in vitro. The flavonoids luteolin, quercetin and fisetin most significantly decreased the amount of myelin phagocytosed by a macrophage cell line without affecting its viability. ic50 values for these compounds ranged from 20 to 80 μM. The flavonoid structure appeared to be essential for observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4 positions in combination with a C-2,3 double bond were most effective. The capacity of the various flavonoids to inhibit phagocytosis correlated well with their potency as antioxidant, which is in line with the requirement of reactive oxygen species for the phagocytosis of myelin by macrophages. Our results implicate that flavonoids may be able to limit the demyelination process during multiple sclerosis.

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