Neurological disorders of iron homeostasis: neurodegeneration with brain iron accumulation (NBIA) and neuroferritinopathies

Arosio Paolo1,*, Dario Finazzi1

1DMMT, University of Brescia, Brescia, Italy

Iron is an essential cofactor for vital enzymes and is also potentially toxic for its capacity to catalyze the generation of aggressive free radicals, therefore its homeostasis must be tightly controlled. Iron is abundant in the brain, mostly in the substantia nigra and in the basal ganglia, and it increases with aging. It increases also in the affected regions in different neurodegenerative disorders, including Alzheimer,  Parkinson disease and in same rare genetic disorders that have been grouped under the name of neurodegeneration with brain iron accumulation (NBIA). They include defects of genes mostly not directly related to iron homeostasis. The exception is neuroferritinopathy a late onset movement disorder that is caused by defects in the ferritin light chain (FTL), a key protein of iron homeostasis. Neuroferritinopathies are a dominant disorder associated with various nucleotide insertions in the last exon of FTL that disrupt the C-terminal part of the molecule and reduce ferritin functionality in iron incorporation. We discuss of  cellular and animal models that showed that the pathogenic mutations of FTL alter cellular iron homeostasis, raise free and redox reactive iron and increase oxidative damage and cell death. Neuroferritinopathies and other NBIAs are important to clarify the relationship between local brain iron accumulation and neurodegeneration  

Keywords: Brain, Inborn error of metabolism