FUNCTIONAL AND EPIDEMIOLOGICAL STUDY OF NEUROFERRITINOPATHIES: IMPLICATIONS FOR THE ROLE OF IRON IN NEURODEGENERATIVE DISORDERS

Neuroferritinopathies are an autosomal dominant genetic disorders linked to two specific mutations of ferritin L-chain, leading to neurodegenerative processes. Ferritin is the major iron storage protein, which is involved in body iron homeostasis. Ferritin is ubiquitous, but the mutation seems to affect specifically the basal ganglia of the brain and to induce iron and protein depositions with probable toxic effects. The disorder indicates a direct relationship between abnormal iron handling in the brain and neurodegeneration, as already suggested by the finding of iron accumulations in the areas of the brain that degenerate in other types of disorders. The study of neuroferritinopathies offers an opportunity to study the regulation of iron homeostasis in the brain, which is not well understood, and lead to the clarification whether the iron is a principal actor or a cofactor in neurodegenerative processes. The research may contribute the understanding of the molecular basis of neurodegenerations. The collaborative work of five groups with complementary expertise in biochemistry, molecular and cellular biology, genetic analysis, neurophysiology and neuroanatomy has the aims: a) to define the molecular mechanisms that cause neurodegeneration in neuroferritinopathy and how relevant are they to the other causes of neurodegeneration, b) to develop animal models to study the ethiopatology and the therapy of the disease, c) to explore the possibility to develop tool to treat this disorder including the use of RNA-interference technologies d) to clarify how common is neuroferritinopathy and if ferritin and iron related proteins are altered in neurodegenerative disorders