Scholarlink

<p>Impaired myelin repair, or remyelination, is a hallmark of progressive multiple sclerosis (MS) that drives brain degeneration and enduring neurological disabilities. Microglia crucially support remyelination through myelin phagocytosis and lipid metabolism. However, in chronic demyelinated MS lesions, microglia lose their reparative function by acquiring a foamy dysfunctional phenotype characterized by accumulation of lipid droplets due to impaired cholesterol processing of myelin debris. Here, we show a positive correlation between dysregulation of neuregulin-1 and impaired oligodendrocyte remyelination in mice with chronic demyelination. Therapeutic restoration of neuregulin-1 fosters myelin regeneration through microglia-dependent mechanisms. We demonstrate that Nrg-1 signaling supports microglia integrity and function in chronic demyelinated lesions by exploiting their capacity for the clearance of myelin debris and cholesterol recycling, biosynthesis and efflux. These findings signify the promise of neuregulin-1 as an endogenous target to facilitate microglia mediated-repair in progressive MS in which there is an unmet need for new treatments.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Neuregulin-1 facilitates myelin regeneration through microglia-mediated mechanisms in a mouse model of chronic demyelination

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月11日

查看全文
  • Seyyed Mohyeddin Ziaee,
  • Shiva Nemati,
  • Hardeep Kataria,
  • Elisabet Jakova,
  • Seyed Mojtaba Hosseini,
  • Pejman Ghelich,
  • Graham McLeod,
  • Ali Tamayol,
  • V. Wee Yong,
  • Soheila Karimi-Abdolrezaee

摘要

Impaired myelin repair, or remyelination, is a hallmark of progressive multiple sclerosis (MS) that drives brain degeneration and enduring neurological disabilities. Microglia crucially support remyelination through myelin phagocytosis and lipid metabolism. However, in chronic demyelinated MS lesions, microglia lose their reparative function by acquiring a foamy dysfunctional phenotype characterized by accumulation of lipid droplets due to impaired cholesterol processing of myelin debris. Here, we show a positive correlation between dysregulation of neuregulin-1 and impaired oligodendrocyte remyelination in mice with chronic demyelination. Therapeutic restoration of neuregulin-1 fosters myelin regeneration through microglia-dependent mechanisms. We demonstrate that Nrg-1 signaling supports microglia integrity and function in chronic demyelinated lesions by exploiting their capacity for the clearance of myelin debris and cholesterol recycling, biosynthesis and efflux. These findings signify the promise of neuregulin-1 as an endogenous target to facilitate microglia mediated-repair in progressive MS in which there is an unmet need for new treatments.