These iron stores are generally regarded as non-damaging and are required for normal brain functions. In the healthy human brain, iron is predominantly stored within the core of ferritin and hemosiderin, in the form of Fe 3+- containing ferrihydrite nanocrystals (Fe 5O 8H) ( Sassi and Rosso, 2019, Dobson, 2001). Molecular specification of the massive iron pool in the aceruloplasminemia brain can aid our understanding of iron related neurodegeneration, and perhaps improve therapeutic considerations, which are currently based on iron chelation.Īmong the molecular forms in which iron can be found in the brain, three are particularly relevant. However, the exact role of different iron forms in the pathophysiology and clinical phenotype of aceruloplasminemia is still not clear.

As a result of ceruloplasmin dysfunction in the brain leading to insufficient cellular iron efflux, iron accumulates within perivascular astrocytes, with total iron concentrations reaching over 600 µg/g in the basal ganglia ( Miyajima, 2015), which is at least five times the normal concentration ( Morita et al., 1995, Miyajima, 2015). Iron accumulation in aceruloplasminemia has been directly linked to its genetic background, as ceruloplasmin-mediated oxidation of ferrous iron (Fe 2+) to ferric iron (Fe 3+) is a prerequisite for transport of iron across cell membranes and for binding to transferrin ( Miyajima et al., 2003). Aceruloplasminemia (OMIM #604290) is a severe adult-onset form of Neurodegeneration with Brain Iron Accumulation (NBIA), caused by homozygous or compound heterozygous mutations in the ceruloplasmin ( CP) gene.

Spacechem postmortem