Editorial: Metals and neurodegeneration: restoring the balance

There is considerable evidence that abnormal biometal homeostasis is a key feature of many neurodegenerative diseases and may have an important role in the onset and progression of disorders such as Alzheimer's (AD), Parkinson's (PD), prion, and motor neuron diseases. The role of biometals in a growing list of brain disorders is supported by evidence from a wide range of sources including molecular genetics, biochemical studies and biometal imaging. These studies have spurred a growing interest in understanding the role of biometals in brain function and disease as well as the development of therapeutic approaches that may be able to restore the altered biometal chemistry of the brain. In this Research Topic, Metals and Neurodegeneration: Restoring the Balance, we probe the biochemical basis of metal-mediated neurodegeneration, examine genetic links between metal dyshomeostasis and brain disorders, investigate metal trafficking and metal-synaptic interactions, and their role in neurodegeneration, and examine some of the key new approaches to understanding how metals drive neurodegenerative changes. We hope that these exciting insights will provide a strong platform to develop advances in therapeutics that will allow us to " restore the balance " in metal homeostasis in the brain. One of the most prominent features across many neurodegenerative disorders is loss of metal homeostasis, and in many cases, the metal revealing the most substantial change is iron (Fe). Opening this Research Topic, Hare et al. (2013) provides an excellent overview of Fe transport and Fe-regulatory processes in the brain, and demonstrates clearly the complexity in these processes. The review describes how abnormalities in this complex process can lead to loss of Fe, which is associated with changes in neurotransmission, energy production and myelination, and is associated with diseases such as AD. Conversely, abnormal Fe handling can also lead to Fe accumulation, which is associated with AD and PD and is a major target of therapeutic developments based on Fe chelation. Expanding on Fe in neurodegeneration is the review by Muhoberac and Vidal (2013), who explore the genetic basis of Fe dyshomeostasis in hereditary ferritinopathy. The article provides a timely insight into the effects of abnormal Fe metabolism through loss of ferritin function, a key Fe-regulatory protein and how these changes can lead to ferritin accumulation, reactive oxygen species formation and oxidative stress. Mariani et al. (2013), further explores hereditary links between Fe and neurodegeneration. They describe links between Fe-specific gene variations (e.g., transferrin, hemochromatosis) and Fe …