About this Research Topic
Iron and copper are important co-factors for a number of enzymes in the brain, including enzymes involved in neurotransmitter synthesis and myelin formation. Both shortage and excess of copper and iron will affect the brain. The transport of copper and iron into the brain from the circulation is strictly regulated and concordantly protective blood-brain and blood-cerebrospinal fluid barriers have evolved to separate the brain environment from the circulation. The sites for uptake and transport of copper and iron into the brain overlap, and the uptake mechanisms of the two metals significantly interact: Both iron deficiency and overload lead to altered copper homeostasis in the brain. Similarly, changes in dietary copper affect the homeostasis of iron in the brain, although a clear understanding on how iron and copper together are handled by neurons and glia, when changes in the availability of these metals occur, has not been sealed.
Inside the brain, the divalent metal transporter-1 (DMT1) is involved in the cellular uptake of both iron and copper. The copper-containing protein ceruloplasmin exhibits ferro-oxidase activity, which is vital for neuronal iron homeostasis. Copper also affects the binding of iron-response proteins to iron-response elements in the mRNA of the transferrin receptor, DMT1, and ferroportin, all highly involved in iron transport. Mutations in genes encoding many proteins related to handling of copper and iron in the brain lead to significant clinical phenotypes. Whereas mutations in genes affecting copper transport and handling by the cells of the brain lead to diseases like Menkes’s disease and Wilson’s disease, results of the recent years have also unraveled mutations in genes related to iron storage due to mutations in the ferritin genes and genetic mutations that collectively leads to the disorder complex known as Neuropathology with Brain Iron Accumulation (NBIA).
The handling of iron- or copper- deficiencies are often manageable with oral or parenteral supplementations, but the appropriate use of the relevant dietary regimens or chelators to treat conditions with robust accumulation of copper or iron would benefit from more knowledge on the mechanisms of actions. e.g. the homeostasis in overload conditions often derives from mishandling at the cellular level that eventually leads to a manifest accumulation at the level of the entire organ calling for very different therapeutic interventions depending on the stage of disease.
Concerning inherited disorders affecting metal-homeostatic mechanisms, more sophisticated strategies, e.g. genetic therapy may be needed to treat single-mutation diseases to support nutritional therapeutic advances.
In this Research Topic of Frontiers in Neuroscience, we welcome researchers to cover topics related to: i) the genetics of proteins handling copper and iron in the brain, ii) the expression and function of copper- and iron proteins in normal and pathological conditions; iii) the clinic manifestations of dietary deficiencies in copper or iron; iv) the clinic manifestation of copper- or iron overload diseases; iv) the clinic manifestation of genetic diseases leading to mishandling of copper and iron, vi) therapeutic aspects of handling dietary deficiencies, overloading pathologies, or conditions with genetic mutations in proteins related to copper and iron.
Inside the brain, the divalent metal transporter-1 (DMT1) is involved in the cellular uptake of both iron and copper. The copper-containing protein ceruloplasmin exhibits ferro-oxidase activity, which is vital for neuronal iron homeostasis. Copper also affects the binding of iron-response proteins to iron-response elements in the mRNA of the transferrin receptor, DMT1, and ferroportin, all highly involved in iron transport. Mutations in genes encoding many proteins related to handling of copper and iron in the brain lead to significant clinical phenotypes. Whereas mutations in genes affecting copper transport and handling by the cells of the brain lead to diseases like Menkes’s disease and Wilson’s disease, results of the recent years have also unraveled mutations in genes related to iron storage due to mutations in the ferritin genes and genetic mutations that collectively leads to the disorder complex known as Neuropathology with Brain Iron Accumulation (NBIA).
The handling of iron- or copper- deficiencies are often manageable with oral or parenteral supplementations, but the appropriate use of the relevant dietary regimens or chelators to treat conditions with robust accumulation of copper or iron would benefit from more knowledge on the mechanisms of actions. e.g. the homeostasis in overload conditions often derives from mishandling at the cellular level that eventually leads to a manifest accumulation at the level of the entire organ calling for very different therapeutic interventions depending on the stage of disease.
Concerning inherited disorders affecting metal-homeostatic mechanisms, more sophisticated strategies, e.g. genetic therapy may be needed to treat single-mutation diseases to support nutritional therapeutic advances.
In this Research Topic of Frontiers in Neuroscience, we welcome researchers to cover topics related to: i) the genetics of proteins handling copper and iron in the brain, ii) the expression and function of copper- and iron proteins in normal and pathological conditions; iii) the clinic manifestations of dietary deficiencies in copper or iron; iv) the clinic manifestation of copper- or iron overload diseases; iv) the clinic manifestation of genetic diseases leading to mishandling of copper and iron, vi) therapeutic aspects of handling dietary deficiencies, overloading pathologies, or conditions with genetic mutations in proteins related to copper and iron.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
