Multiple sclerosis (MS) is a progressive inflammatory disease of the central nervous
system (CNS) leading to severe neurological deficits. To date, no treatment is available that
halts disease progression, but clinical symptoms can be generally improved by therapies
involving anti-inflammatory and/or immune modulatory reagents, which may cause off-target
effects. Therefore, there remains a high and unmet need for more selective treatment strategies
An early event in MS is a diminished function of the blood-brain barrier (BBB) which consists
of specialized brain endothelial cells (BECs) that are supported in their barrier function by
surrounding glial cells.
Leakage and inflammation of the BECs in MS patients facilitate the massive influx of leukocytes into the brain
parenchyma, which in turn induces irreversible demyelination, tissue damage and axonal dysfunction. Identification of
ways to restore BBB function and promote its immune quiescence may therefore lead to the development of novel
therapeutic regimes that not only specifically reduce leukocyte entry into the central nervous system but also restore the
disturbed brain homeostasis. However, the complex network of molecular players that leads to BBB dysfunction in MS is
yet to be fully elucidated. Recent discoveries unravelled a critical role for microRNAs (miRNAs) in controlling the
function of the barrier endothelium in the brain. Here we will review the current knowledge on the involvement of BBB
dysfunction in MS and the central role that miRNAs play in maintaining BBB integrity under inflammatory conditions.