Perturbation of
iron distribution is observed in many
neurodegenerative disorders, including Alzheimer's and
Parkinson's disease, but the comprehension of the
metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic
DNA sequencing procedures has allowed the description of a set of
genetic disorders characterized by a constant and often early accumulation of
iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of
neurodegeneration with brain iron accumulation (NBIA). So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in
iron metabolism:
neuroferritinopathy, associated to mutations in the FTL gene and
aceruloplasminemia, where the
ceruloplasmin gene product is defective. In the other forms the connection with
iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, Pla2G6, C19orf12, COASY, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a
nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain
iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common
neurodegenerative disorders. In this work, we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain
iron metabolism.