Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration.

Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells - astrocytes and mature myelin-forming oligodendrocytes - is a determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models, unbiased RNA sequencing, functional manipulation, and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation.

Microglia as therapeutic targets for central nervous system remyelination.

Failed remyelination underpins neurodegeneration and central nervous system (CNS) dysfunction with aging and progression of neurological diseases, such as multiple sclerosis and Alzheimer's disease. Existing therapies have shown limited efficacy in halting disease progression in humans, highlighting the need to identify pro-remyelination treatments. Microglia are CNS-resident macrophages with critical roles in the regulation of remyelination, representing a promising therapeutic target.