Preliminary clinical trials also support a key role for uric acid in the pathogenesis of early onset essential hypertension. An open-label pilot study was conducted in 5 children with newly diagnosed, untreated essential hypertension. They were treated with allopurinol for 4 weeks followed by a 6-week washout period. Since its discovery, much of the research of the type 1 transmembrane protein bamyloid precursor protein has focused on its proteolytic BAY 73-4506 components, particularly the b-amyloid peptide that accumulates in Alzheimer’s disease. However, full length APP is yet to be attributed a conclusive function. It has been described to have roles in transcriptional signaling, synapse formation, ion transport, neuroprotection and neuroplasticity. Recently we have added to this growing functional list by reporting that both the full-length membrane bound and the cleaved soluble extracellular form of sAPPa, but not other family members amyloid precursor-like protein 1 and 2, facilitate the efflux of iron from APP-expressing cells such as neurons. As an integral cofactor in many metabolic processes, iron must be closely regulated for the wellbeing of any cell, particularly where oxygen consumption is high such as in the neuron. The ability for iron to undergo redox-cycling is harnessed by some enzymes for catalysis, however under aerobic conditions iron may also catalyze the production of reactive oxygen species through the Haber-Weiss and Fenton reactions. Unregulated hydroxyl radical and ROS production is damaging to the cell and have been associated with aging and disease, particularly in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and aceruloplasminemia, where iron accumulates in affected tissue. As both iron deficiency or excess may compromise cell viability, homeostasis is tightly controlled with cell entry, storage and exit. Import of iron was previously considered to be solely through either divalent metal transporter 1 or by transferrin import through interaction with the Transferrin Receptor. However, other import mechanisms have now been described including ZIP14, indicating that uptake of iron into the cell may not be as simple as previously thought. Currently, there is only one known iron export pore protein, ferroportin, which is believed to traffic Fe2+ from the cytoplasm to the plasma membrane surface. While a variety of mechanisms are thought to facilitate the release of iron from the exofacial surface of FPN, multicopper ferroxidases such as ceruloplasmin, hephaestin and the bacterial ferroxidase Fet3, were previously considered the only facilitators of intracellular iron efflux. This was mediated through their ability to secure Fe2+ from stabilized FPN on the cell surface and promote Fe2+ oxidation for Fe3+ loading into iron-transporting proteins such as transferrin. We concluded that APP might also fulfill an analogous function for iron release. We found that the major proportion of APP in human and mouse postmortem brain tissue samples is complexed to FPN, and that APP knockout mice markedly accumulate iron in several organs, including the brain. Several reports have since corroborated the impact of APP expression on cellular iron levels.