Role of redox and ceruloplasmin in iron deposition in glial cells: Implication in neurodegenerative damages

The cellular oxidation and reduction (redox) environment is influenced in presence of transition metals mainly iron and copper. They are also part of the regimen responsible for production and removal of reactive oxygen species (ROS). Interestingly, in most of the neurodegenerative diseases increased ROS generation and iron deposition were detected. However, their intrinsic relations either to cause the pathogenic condition found in neurodegenerative diseases or they are produced as a result of the condition is not clear yet. The human brain comprises only 2% of the total body weight, yet it is especially prone to ROS generation as it consumes about 20% of the resting total body oxygen. Similarly, need of glucose is also higher in active brain. Both the oxygen metabolism and glucose metabolism to gain energy are highly dependent on cellular iron metabolism. However, brain iron metabolism is so far less understood compare to the other organs. Since, ROS in presence of excess iron is highly reactive to cause oxidative damage, expression of iron homeostasis genes are usually regulated to avoid their proximity to each other. Glial cells play important role in movements of nutrients including essential metals like iron and copper to neurons as well as controlling ROS generation. Thus, it is important to understand the iron homeostasis components of glial cells in order to understand the role of redox/ROS and iron/copper mediated neurodegeneration. Ceruloplasmin (Cp) as a multicopper protein having ferroxidase (Fe ₂+ to Fe ₃+) activity performs a central role in body iron homeostasis. It has been described both as an antioxidant and oxidant molecule. In mammals, astroglia contains specialized membrane bound glycosyl-phosphatidyl-inositol (GPI)- anchored form of Cp that plays an important role in iron metabolism in central nervous system (CNS) by regulating iron release by maintaining stability of ferroportin. Mutation in Cp leads to iron deposition in various regions of CNS. All these evidences show a crucial role of Cp in maintaining body iron homeostasis including CNS. Here, we discuss the regulation of GPI-Cp by ROS that may be one of the potential mechanisms of iron deposition in glial cells.