Hiroaki Miyajima

By Hiroaki Miyajima

In neurons, iron plays an important role in the signal transduction related to synaptic plasticity. The neuronal iron supply is tightly controlled and depends not only on transferrin-bound iron but also on non-transferrin-bound iron (NTBI). Ceruloplasmin is bound to the cell membranes of astrocytes, where it plays a role in iron efflux from astrocytes due to the activity of ferroxidase, which oxidizes ferrous iron after its transfer to the cell surface via ferroportin, and which delivers ferric iron to extracellular transferrin, which is transported to neurons. Aceruloplasminemia is an autosomal recessive neurodegenerative disorder in which iron accumulates in the brain due to the complete lack of ceruloplasmin ferroxidase activity. Redox-active iron accumulation was found to be more prominent in astrocytes than in neurons. Neurons take up iron from alternative sources of NTBI because astrocytes without ceruloplasmin cannot transport iron to transferrin. Neuronal cell loss may result from iron starvation in the early stage of aceruloplasminemia and may result from iron-mediated oxidation in the late stage of the condition. The excess iron in astrocytes can result in oxidative damage to these cells, thereby disrupting the neuronal cell protection offered by astrocytes in patients with aceruloplasminemia.

Part of the book: Astrocyte