Iron in the brain (with apologies to Jean-Paul Sartre): Heavy metal mismanagement

Iron’s activity in the body can be two-faced. On the one hand it is integral to many enzymatic reactions; on the other hand it is toxic, with a great capacity for cellular damage. This review examines iron in the brain through the lens of multiple sclerosis (MS), reviewing the functions of intracellular and extracellular iron and their impact on the disease, as well as highlighting the focus of new research and controversial therapies. The primary cause of MS has remained enigmatic, ever since its first clinical documentation. Several studies have suggested a link between MS and iron. Abnormal iron accumulation has been found as deposits in MS lesions around cerebral veins, in the macrophages surrounding MS lesions, and also in deep brain structures. There are features of MS, such as the inflammatory environment and altered vasculature, which are important in highlighting mechanisms of how iron can accumulate, and also how iron dysregulation can create a positive feedback cycle that further promotes neurodegeneration and increased iron accumulation. This potential link between iron and MS has gained widespread attention, in part due to the controversial cerebrospinal venous insufficiency (CCSVI) hypothesis and “Liberation Therapy” first introduced by Dr. Zamboni in 2008. Determining the role of iron in MS will help provide a better insight to the different factions of scientists who disagree on whether MS is primarily an autoimmune disorder, or whether a neurodegenerative mechanism is the instigator.