Grant: Operating Grant

Iron is essential for life. It plays an important role in the functioning of enzymes required for a whole host of cellular functions. However, iron can also generate toxic free radicals that can damage cells if it is not properly handled. Therefore, although iron accumulation results in free-radical-mediated cell death, lack of cellular iron can also lead to loss of cell viability. In the central nervous system (CNS) which consists of the brain and spinal cord, iron is required for the survival of neurons. It is also required for myelination which is essential for proper conduction of nerve impulses. How iron from the circulation is delivered to different cell types in the nervous system is still not fully understood. A number of molecules that transport and detoxify iron are involved in the safe delivery of iron from one cell type to another. The aim of this proposal is to study the role of an iron transporter called ferroportin, two ferroxidases called hephaestin and ceruloplasmin, and an iron binding protein called lipocalin 2, in iron trafficking in the nervous system. This work has important implications for various neurodegenerative diseases in which iron accumulation occurs as well as for neuropathies that affect peripheral nerves.