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Pathogenic mechanism and modeling of neuroferritinopathy

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Abstract

Neuroferritinopathy is a rare autosomal dominant inherited movement disorder caused by alteration of the L-ferritin gene that results in the production of a ferritin molecule that is unable to properly manage iron, leading to the presence of free redox-active iron in the cytosol. This form of iron has detrimental effects on cells, particularly severe for neuronal cells, which are highly sensitive to oxidative stress. Although very rare, the disorder is notable for two reasons. First, neuroferritinopathy displays features also found in a larger group of disorders named Neurodegeneration with Brain Iron Accumulation (NBIA), such as iron deposition in the basal ganglia and extrapyramidal symptoms; thus, the elucidation of its pathogenic mechanism may contribute to clarifying the incompletely understood aspects of NBIA. Second, neuroferritinopathy shows the characteristic signs of an accelerated process of aging; thus, it can be considered an interesting model to study the progress of aging. Here, we will review the clinical and neurological features of neuroferritinopathy and summarize biochemical studies and data from cellular and animal models to propose a pathogenic mechanism of the disorder.

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Acknowledgments

The financial support from TELETHON-ITALIA (Grant Nos. GGP10099, GGP11088 and GGP16234 to SL) and AISNAF (to SL) is gratefully acknowledged.

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Authors and Affiliations

  1. Proteomic of Iron Metabolism Unit, Division of Neuroscience, San Raffaele Scientific Institute, 20132, Milan, Italy

    Anna Cozzi, Paolo Santambrogio, Maddalena Ripamonti & Sonia Levi

  2. Institute for Genetic and Biomedical Research, National Research Council, 20138, Milan, Italy

    Ermanna Rovida

  3. Vita-Salute San Raffaele University and San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy

    Sonia Levi

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  1. Anna Cozzi
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  2. Paolo Santambrogio
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  3. Maddalena Ripamonti
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  5. Sonia Levi
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Correspondence to Sonia Levi.

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Cozzi, A., Santambrogio, P., Ripamonti, M. et al. Pathogenic mechanism and modeling of neuroferritinopathy. Cell. Mol. Life Sci. 78, 3355–3367 (2021). https://doi.org/10.1007/s00018-020-03747-w

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  • DOI: https://doi.org/10.1007/s00018-020-03747-w

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