Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-58862
Science 2022 Feb 18;3756582:eabm4459. doi: 10.1126/science.abm4459.
Show Gene links Show Anatomy links

Engineered Wnt ligands enable blood-brain barrier repair in neurological disorders.

Martin M, Vermeiren S, Bostaille N, Eubelen M, Spitzer D, Vermeersch M, Profaci CP, Pozuelo E, Toussay X, Raman-Nair J, Tebabi P, America M, De Groote A, Sanderson LE, Cabochette P, Germano RFV, Torres D, Boutry S, de Kerchove d'Exaerde A, Bellefroid EJ, Phoenix TN, Devraj K, Lacoste B, Daneman R, Liebner S, Vanhollebeke B.


???displayArticle.abstract???
The blood-brain barrier (BBB) protects the central nervous system (CNS) from harmful blood-borne factors. Although BBB dysfunction is a hallmark of several neurological disorders, therapies to restore BBB function are lacking. An attractive strategy is to repurpose developmental BBB regulators, such as Wnt7a, into BBB-protective agents. However, safe therapeutic use of Wnt ligands is complicated by their pleiotropic Frizzled signaling activities. Taking advantage of the Wnt7a/b-specific Gpr124/Reck co-receptor complex, we genetically engineered Wnt7a ligands into BBB-specific Wnt activators. In a "hit-and-run" adeno-associated virus-assisted CNS gene delivery setting, these new Gpr124/Reck-specific agonists protected BBB function, thereby mitigating glioblastoma expansion and ischemic stroke infarction. This work reveals that the signaling specificity of Wnt ligands is adjustable and defines a modality to treat CNS disorders by normalizing the BBB.

???displayArticle.pubmedLink??? 35175798
???displayArticle.link??? Science
???displayArticle.grants??? [+]

Species referenced: Xenopus laevis
Genes referenced: wnt7a
GO keywords: Wnt signaling pathway [+]

???displayArticle.disOnts??? glioblastoma
???displayArticle.omims??? STROKE, ISCHEMIC