👤 Merel Rijnsburger

To date, available treatment strategies for multiple sclerosis (MS) are ineffective in preventing or reversing progressive neurologic deterioration, creating a high, and unmet medical need. One potential way to fight MS may be by limiting the detrimental effects of reactive astrocytes, a key pathological hallmark for disease progression. One class of compounds that may exert beneficial effects via astrocytes are melanocortin receptor (MCR) agonists. Among the MCR, MC4R is most abundantly expressed in the CNS and several rodent studies have described that MC4R is-besides neurons-expressed by astrocytes. Activation of MC4R in astrocytes has shown to have potent anti-inflammatory as well as neuroprotective effects Show less

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) characterized by the presence of focal demyelinated plaques. Sufficient clearance of myelin and cellular debris is one of the requirements for proper tissue repair and remyelination. The mechanisms underlying the clearance of such debris by phagocytes are not fully understood, but recent findings suggest a prominent role for lipoprotein-lipase (LPL) in this process. Here, we demonstrate that angiopoietin-like 4 (ANGPTL4), a potent inhibitor of LPL, is abundantly expressed in astrocytes in control white matter tissue and its expression is markedly reduced in active MS lesions. We provide evidence that ANGPTL4 inhibits the uptake of myelin-derived lipids by LPL-immunoreactive phagocytes. Taken together, our data suggest that the strong reduction in astrocytic ANGPTL4 expression in active demyelinating MS lesions enables phagocytes to adequately clear myelin debris, setting the stage for remyelination. Show less