Neuroferritinopathy: a neurodegenerative disorder associated with L-ferritin mutation.
Neuroferritinopathy is a dominantly inherited movement disorder characterized by deposition of iron and ferritin in the brain, normal or low serum ferritin levels, and highly variable clinical features. The disease, also named dominant adult-onset basal ganglia disease, is associated with a nucleotide insertion that modifies the last 22 amino acids of the ferritin L-chain. A similar dominant movement disorder in a French family was associated with a nucleotide insertion that modifies the last nine amino acids of the same molecule. Both disorders show ferritin and iron precipitates in the basal ganglia of the brain. Here we present the structural aspects of the two mutations, as well studies on cellular models aimed at understanding the molecular basis of the disorder. The results indicate that the mutations affect protein folding and stability, and that the expression of one of the two variant ferritins increases intracellular iron availability and sensitivity to oxidative damage.
Levi
Sonia
S
Department of Biological and Technological Research, IRCCS H. San Raffaele, Via Olgettina 58, Milano, 20132 Italy. levi.sonia@hsr.it
Cozzi
Anna
A
Arosio
Paolo
P
D001052:Apoferritins; D001480:Basal Ganglia Diseases / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D005293:Ferritins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005799:Genes, Dominant; D006801:Humans; D007501:Iron / Q000378:metabolism; D009069:Movement Disorders / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D017433:Protein Structure, Secondary
D005293:Ferritins; D001052:Apoferritins; D007501:Iron