Animal models of neuroferritinopathies for the study of the role of iron in neurodegeneration

Neuroferritinopathies are autosomal dominant genetic disorders linked to specific mutations of ferritin L-chain, that lead to brain iron accumulation and neurodegenerative processes. Ferritin has a major role in the regulation of body iron homeostasis and it has been demonstrated that its capacity to store iron in a non-toxic form is reduced by the mutations that cause neuroferritinopathy. The study of these pathologies offer an opportunity to obtain novel information on the regulation and toxicity of iron in the brain, to clarify the mechanisms affected tby the iron excess that lead to neurtpdegeneration. The collaborative work of five groups with complementary expertise in biochemistry, molecular and cellular biology, neurophysiology and neuroanatomy has the aim to study the molecular mechanisms that cause neurodegeneration in these diseases and to understand how to prevent them and cure them. The project is mainly based on the characterization and improvement of the neuroferritinopathy animal models already developed. It will involve the study of the functional, structural and biochemical characteristics of the brain of the transgenic mice the express the pathogenic mutant ferritins, the properties of the cells obtained from the mice, and the reaction mecahsnims of the reactions in which the mutant ferritin participate. Moreover, it will include therapeutic strategies to reduce brain iron accumulation and neurodegeneration.