alkyl-glycerol rescues plasmalogen levels and pathology of ether-phospholipid deficient micealkyl-glycerol救援缩醛磷脂水平和病理学ether-phospholipid缺乏的老鼠.pdfVIP

Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice 1,2 2 1,3 1,3 1 Pedro Brites *, Ana Sofia Ferreira , Tiago Ferreira da Silva , Vera F. Sousa , Ana R. Malheiro , 2 2 4 2 Marinus Duran , Hans R. Waterham , Myriam Baes , Ronald J. A. Wanders 1 Nerve Regeneration Group, Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal, 2 Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 3 ICBAS, Universidade do Porto, Porto, Portugal, 4 Laboratory for Cell Metabolism, Department of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Leuven, Belgium Abstract A deficiency of plasmalogens, caused by impaired peroxisomal metabolism affects normal development and multiple organs in adulthood. Treatment options aimed at restoring plasmalogen levels may be relevant for the therapy of peroxisomal and non-peroxisomal disorders. In this study we determined the in vivo efficacy of an alkyl glycerol (AG), namely, 1-O-octadecyl- rac-glycerol, as a therapeutic agent for defects in plasmalogen synthesis. To achieve this, Pex7 knockout mice, a mouse model for Rhizomelic Chondrodysplasia Punctata type 1 characterized by the absence of plasmalogens, and WT mice were fed a control diet or a diet containing 2% alkyl-glycerol. Plasmalogen levels were measured in target organs and the biochemical data were correlated with the histological analysis of affected organs. Plasmalogen levels in all peripheral tissues of Pex7 KO mice fed the AG diet for 2 months normalized to the levels of A