%0 Journal Article
%T Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation
%A Anthony Drecourt
%A Arnold Munnich
%A Chris Ottolenghi
%A Christine Bole-Feysot
%A Florence Habarou
%A Floriane Petit
%A Isabelle Desguerre
%A Jo£¿l Babdor
%A Meriem Garfa-Traor¨¦
%A Metodi D. Metodiev
%A Michael Dussiot
%A Nathalie Boddaert
%A Nicolas Goudin
%A Olivier Hermine
%A Patrick Nitschk¨¦
%A Val¨¦rie Serre
%J Archive of "American Journal of Human Genetics".
%D 2018
%R 10.1016/j.ajhg.2018.01.003
%X Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous condition characterized by progressive dystonia with iron accumulation in the basal ganglia. How NBIA-associated mutations trigger iron overload remains poorly understood. After studying fibroblast cell lines from subjects carrying both known and unreported biallelic mutations in CRAT and REPS1, we ascribe iron overload to the abnormal recycling of transferrin receptor (TfR1) and the reduction of TfR1 palmitoylation in NBIA. Moreover, we describe palmitoylation as a hitherto unreported level of post-translational TfR1 regulation. A widely used antimalarial agent, artesunate, rescued abnormal TfR1 palmitoylation in cultured fibroblasts of NBIA subjects. These observations suggest therapeutic strategies aimed at targeting impaired TfR1 recycling and palmitoylation in NBIA
%K neurodegeneration with brain iron accumulation
%K NBIA
%K iron overload
%K transferrin receptor
%K palmitoylation
%K mitochondria
%K artesunate
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985451/