Dysregulated copper transport in multiple sclerosis may cause demyelination via astrocytes

Significance This study describes an astrocyte-dependent mechanism contributing to CNS demyelination. The key molecular and functional checkpoint is the neurotrophin receptor TrkB, whose ligands are absent in chronic demyelinated MS lesions. Here, we show that TrkB can be transactivated by inflammatory and toxic signals and is critical for the generation of glial calcium flux and the up-regulation of the copper transporter CTR1. This process enhances copper distribution by the astrocyte, thereby fostering myelin and oligodendrocyte loss.