Neurodegeneration with Brain Iron Accumulation Disorders: Valuable Models Aimed at Understanding the Pathogenesis of Iron Deposition

Abstract

Neurodegeneration with brain iron accumulation (NBIA) is a set of neurodegenerative disorders, which includes very rare monogenetic diseases. They are heterogeneous in regard to the onset and the clinical symptoms, while the have in common a specific brain iron deposition in the region of the basal ganglia that can be visualized by radiological and histopathological examinations. Nowadays, 15 genes have been identified as causative for NBIA, of which only two code for iron-proteins, while all the other causative genes codify for proteins not involved in iron management. Thus, how iron participates to the pathogenetic mechanism of most NBIA remains unclear, essentially for the lack of experimental models that fully recapitulate the human phenotype. In this review we reported the recent data on new models of these disorders aimed at highlight the still scarce knowledge of the pathogenesis of iron deposition.

Keywords: NBIA; iron; neurodegeneration.

Figure 1

Scheme of the proteins associated to NBIA disorders and their cellular localization. The iron proteins (CP and FtL) are represented in light blue; in pink are the proteins (PANK2 and COASY) are involved in CoA synthesis; in yellow are the proteins related to lipid metabolism (PLA2G6, FA2H, SCP2, CRAT, C19orf12); in orange are the proteins (WDR45, ATP13A2) involved in autophagy; in grey are the proteins (RESP1 and AP4M1) associated to vesicle trafficking; and the proteins (DCAF17 and GTPBP2) in green still have unknown functions.