title: [ManNAc, a new therapeutic agent to reduce Angptl4-induced proteinuria in MCD].
abstract: Current therapies used in minimal change disease (MCD) were originally designed to cure other diseases. They are only partially efficient, and present inconvenient side effects. Therefore, understanding the molecular mechanisms implicated in the pathogenesis of proteinuria in MCD could lead to new therapeutic strategies. A new experimental transgenic rat model of human MCD was generated. These NPHS2-Angptl4 transgenic rats over-express two different forms of the glycoprotein Angptl4 from the podocyte. The majority of the protein shows a lack of sialylation that is implicated in the pathogenesis of proteinuria. Supplementation of ManNAc, a precursor of sialic acid, significantly reduces albuminuria in those rats by increasing sialylation of the hyposialylated form of Angptl4. After treatment of the first episode of MCD with glucocorticoids in patients, ManNAc could be used as a maintenance drug, especially to reduce the frequency and intensity of relapse. ManNAc is a promising therapeutic agent for patients with MCD.
authors.affiliation: Glomerular disease therapeutics laboratory, Medicine/Division of Nephrology, university of Alabama at Birmingham, 1900 University boulevard, THT 611N, Birmingham, AL 35294, Étas-Unis.
authors.forename: Lionel
authors.initials: L
authors.lastname: Clément
authors.affiliation: Glomerular disease therapeutics laboratory, Medicine/Division of Nephrology, university of Alabama at Birmingham, 1900 University boulevard, THT 611N, Birmingham, AL 35294, Étas-Unis.
authors.forename: Camille
authors.initials: C
authors.lastname: Macé
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000235:genetics*; D000818:Animals; D006595:Hexosamines / Q000627:therapeutic use*; D006801:Humans; D009402:Nephrosis, Lipoid / Q000235:genetics / Q000628:therapy*; D009404:Nephrotic Syndrome / Q000235:genetics / Q000628:therapy; D011507:Proteinuria / Q000235:genetics*; D051381:Rats; D055647:Rats, Transgenic; D035703:Therapies, Investigational
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D006595:Hexosamines; C002022:N-acetylmannosamine