A mouse model of glioblastoma multiforme was used to determine the accumulation of a targeted contrast agent in tumor vessels. The contrast agent, consisting of superparamagnetic iron oxide coated with dextran, was functionalized with an anti-insulin-like-growth-factor binding protein 7 (anti-IGFBP7) single domain antibody. The near infrared marker, Cy5.5, was also attached for an in vivo fluor...

Neurotoxicity in all prion disorders is believed to result from the accumulation of PrP-scrapie (PrP(Sc)), a beta-sheet rich isoform of a normal cell-surface glycoprotein, the prion protein (PrP(C)). Limited reports suggest imbalance of brain iron homeostasis as a significant associated cause of neurotoxicity in prion-infected cell and mouse models. However, systematic studies on the generality...

Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by mutations in the ceruloplasmin gene. Its prevalence is 1 in 2,000,000 people in Japan. This is a disorder of neurodegeneration with iron accumulation in the brain revealed by MRI. The iron overload induces oxidative stress and generation of reactive oxygen species, which triggers a cascade of pathological events ...

BACKGROUND Neurodegeneration with brain iron accumulation (NBIA), formerly known as Hallervorden-Spatz syndrome, is a heterogeneous group of disorders with different treatment options. CASE REPORTS In the first case, progressively generalizing dystonic symptoms appeared during childhood. A mutation in the gene encoding pantothenate kinase 2 (PANK2) was found. Brain MRI showed bilateral hypers...

We previously demonstrated that cultured human fibroblasts internalize iron via transferrin-independent iron uptake (Tf-IU), redox, and receptor-mediated endocytosis uptake systems [Oshiro, S., Nakajima, H., Markello, T., Krasnewich, D., Bernardini, I., and Gahl, W.A. (1993) J. Biol. Chem. 268, 21586 21591]. Of these iron transport systems, the Tf-IU system is involved in the accumulation of tr...

The principal infectious and pathogenic agent in all prion disorders is a beta-sheet-rich isoform of the cellular prion protein (PrP(C)) termed PrP-scrapie (PrP(Sc)). Once initiated, PrP(Sc) is self-replicating and toxic to neuronal cells, but the underlying mechanisms remain unclear. In this report, we demonstrate that PrP(C) binds iron and transforms to a PrP(Sc)-like form (*PrP(Sc)) when hum...

Metal ions accumulate in the brain with aging and in several neurodegenerative diseases. Aside from the copper storage disease, Wilson's disease, recent attention has focused on the accumulation of zinc, copper and iron in the Alzheimer's disease (AD) brain and the accumulation of iron in Parkinson's disease. In particular, the parenchymal deposition of beta-amyloid (Abeta) and its interaction ...

Neuroferritinopathy is an autosomal dominant extrapyramidal movement disorder, caused by FTL gene mutations. Iron decreases the MR T2* decay time, therefore increasing the R2* (R2* = 1 /T2*), which correlates with brain tissue iron content. 3T structural and quantitative MR imaging assessment of R2* in 10 patients with neuroferritinopathy demonstrated a unique pattern of basal ganglia cavitatio...