Chiral 1,4-oxazepan-3-one Targeting Schwann Cells Exhibits Morphometrically Inhibitory Effects on Wallerian Degeneration
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초록
Schwann cell is a unique neuroglial cell and has essential functions for regulating Wallerian degeneration and peripheral nerve regeneration after nerve injury. When Wallerian degeneration is inefficient or irreversible due to non-function or malfunction of Schwann cells, peripheral nerve regeneration doesn’t occur and peripheral neurodegenerative diseases are induced, such as diabetic neuropathies. However, effective medicinal therapeutics has not been developed. In this study, we employed a synthesized chiral 1,4-oxazpan-3-one (1,4-DZ) compound to investigate neuroanatomically degenerative characteristics of Schwann cells during Wallerian degeneration. We also used ex vivo sciatic nerve explant system to exclude macrophage effects on demyelination, performed immunostaining by using teased nerve fiber samples to observe the outlook of myelin sheath during Wallerian degeneration, and identified its inhibitory effects on the degeneration. Thus, our results suggested that 1,4-DZ could be a prototype to develop a new small drug for peripheral neurodegenerative diseases.
Abstract
Schwann cell is a unique neuroglial cell and has essential functions for regulating Wallerian degeneration and peripheral nerve regeneration after nerve injury. When Wallerian degeneration is inefficient or irreversible due to non-function or malfunction of Schwann cells, peripheral nerve regeneration doesn’t occur and peripheral neurodegenerative diseases are induced, such as diabetic neuropathies. However, effective medicinal therapeutics has not been developed. In this study, we employed a synthesized chiral 1,4-oxazpan-3-one (1,4-DZ) compound to investigate neuroanatomically degenerative characteristics of Schwann cells during Wallerian degeneration. We also used ex vivo sciatic nerve explant system to exclude macrophage effects on demyelination, performed immunostaining by using teased nerve fiber samples to observe the outlook of myelin sheath during Wallerian degeneration, and identified its inhibitory effects on the degeneration. Thus, our results suggested that 1,4-DZ could be a prototype to develop a new small drug for peripheral neurodegenerative diseases.
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