Proteomic of iron metabolism

Proteomic of iron metabolism

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Group leader

Sonia Levi

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The unit studied, from a functional, structural and immunological standpoint, proteins involved in iron metabolism and diseases associated with them. In recent years, the main research lines followed in the unit are focused to the study of mitochondrial iron metabolism and the understanding of the role of iron in neurodegenerative processes.

Research activity

The group dealt with the development of cellular and animal models for the study of rare diseases characterized by the presence of brain iron accumulation, or NBIA (Neurodegeneration with Brain Iron Accumulation). Several genes have been identified as causative of NBIA, pathologies classified as extrapiramidal movement disorders with variable age of onset. The aim is to identify, from the different forms of NBIA, the probable common pathological events that give rise to the brain iron accumulation phenotype. Presently the group is studying the iron metabolism alterations in patients suffering from PKAN, CoPAN and neuroferritinopathy. PKAN is one of the most frequent form among the NBIA and caused by mutation in PANK2. CoPAN is caused by mutations in COASY and  neuroferritinopathy is caused by mutations in the gene codifying L-ferritin, FTL1.

The unit is using the cellular reprogramming methodologies to develop new human neuronal models, useful to examine the alteration of the iron metabolism in these pathologies. In the recent years, the Unit obtained and characterized human induced pluripotent stem cells (hiPSC) derived from patients suffering from PKAN, CoPAN and neuroferritinopathy. These hiPSC are currently differentiated in neurons and astrocytes and utilized to investigate the process of iron accumulation. These new models represent a powerful in vitro model system in which to investigate and dissect early molecular events, eventually accumulating and giving rise to degeneration or death of neuronal cells. In addition, the studies on these cellular models allow to identify possible therapeutic targets and to test in vitro efficacy of specific compounds.