| Literature DB >> 29395073 |
Anthony Drecourt1, Joël Babdor1, Michael Dussiot1, Floriane Petit2, Nicolas Goudin3, Meriem Garfa-Traoré3, Florence Habarou4, Christine Bole-Feysot2, Patrick Nitschké2, Chris Ottolenghi4, Metodi D Metodiev2, Valérie Serre5, Isabelle Desguerre6, Nathalie Boddaert7, Olivier Hermine1, Arnold Munnich7, Agnès Rötig8.
Abstract
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.Entities:
Keywords: NBIA; artesunate; iron overload; mitochondria; neurodegeneration with brain iron accumulation; palmitoylation; transferrin receptor
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Year: 2018 PMID： 29395073 PMCID： PMC5985451 DOI： 10.1016/j.ajhg.2018.01.003
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025