The earliest and most proximal triggers of inflammatory demyelination in multiple sclerosis (MS) remain an open question. In this DNACB review we address experimental and clinical evidence consistent with subtle perturbations of the axo-myelinic compartment of central nervous system white matter as initiation sites of secondary autoimmune demyelination in MS. Strengthened by experimental evidence that by inhibiting myelinopathy one can prevent inflammatory demyelination, myelin-protective therapies may represent a new class of anti-inflammatory medications for combating myelin autoimmunity.
Keywords: autoimmune triggers; citrullination; inflammatory demyelination; multiple sclerosis; myelin compaction; neuroinflammation.