The central nervous system (CNS) is one of the highest energy-consuming tissues in the body. Therefore, demand for iron, which is an important cofactor for mitochondrial oxidative phosphorylation, is also high. Most of the key proteins involved in peripheral iron homeostasis also exist in the CNS. However, it has its own unique regulatory mechanism because the CNS is isolated by the blood-brain-barrier (BBB). Currently, it is not clear how different brain cell types communicate with one another to maintain global brain iron homeostasis. Nor do we know the crosstalk mechanism between the CNS and the rest of the body to control iron absorption.
NBIA is a collection of neurodegenerative diseases with common features, including localized iron accumulation in brain. For most NBIA disorders, excluding aceruloplasminemia and neuroferritinopathy, the known functions of the disease genes are not directly associated with iron metabolism, and it is not known how these mutations lead to brain iron accumulation. Due to the redox-active nature of iron, excessive and misregulated iron can cause toxic effects in cells and tissue, eventually leading to neurodenegeration. New experiments led by Dr. Suh Young Jeong will study how mutations in PANK2, the disease gene for PKAN, cause iron accumulation in cells and lead to cell death using both in vitro and in vivo models.