Apolipoproteïne D, een nieuw ligand voor CD36, is essentieel voor de bloed-hersenbarrière

BACKGROUND:The disruption of the blood–brain barrier (BBB) is a central pathogenic event in many central nervous system disorders. However, the mechanisms regulating BBB function remain incompletely understood, and effective treatments are lacking. Brain mural cells differ significantly from their peripheral counterparts, a distinction likely critical for maintaining BBB integrity.METHODS:We combined proteomic profiling of human brainvsperipheral mural cells with multiple ischemic stroke models (global apolipoprotein D [ApoD] knockout, mural cell–specific ApoD knockout, and adeno-associated virus–mediated ApoD overexpression) to evaluate the role of ApoD in BBB integrity. Mechanistic studies (co-immunoprecipitation, binding assays, including surface plasmon resonance, bio-layer interferometry, cross-linking mass spectrometry, and CD36 loss-of-function approaches, both in vitro and in vivo) were performed to determine how ApoD interacts with CD36 and inhibits its signaling. Finally, we