Editorial: [Hot Topic The Biochemistry/Toxicity of Aluminum (Guest Editors: Christopher A. Shaw & Lucija Tomljenovic)]

We live in what one author of this Hot Topic issue has correctly labeled “the Age of Aluminum” [1]. Aluminum, the third most abundant element in the Earth's crust and the most abundant metal, is one of the most remarkable elements in the periodic table. Compounds made with aluminum are strong, durable, light and corrosion resistant. Aluminum is also an excellent conductor of electricity. For these reasons, aluminum currently finds its way into virtually every aspect of our daily lives. Industrially, aluminum is used in cans and cookware, aluminum foil, housing materials, components of electrical devices, airplanes, boats, cars and numerous hardware items of all descriptions. Aluminum is found in drinking water, as a food additive in typical Western diets, cosmetics, pharmaceutical products and because of such ubiquity, it is increasingly found in our bodies [2, 3]. None of this would necessarily be a problem if aluminum was inert in biological systems. However, in spite of a widely held belief that this is true, it is demonstrably not the case. Aluminum is highly reactive with oxygen and carbon, two of the most abundant organic elements, yet appears to have no intrinsic nor beneficial role in organic chemistry of any biota on the planet [1]. Instead, evidence clearly shows that aluminum is toxic to plants, animals and humans. For example, aluminum intoxication frequently impairs learning, memory, concentration and behaviour in both animals and humans. The latter is typically reflected in confusion, anxiety, repetitive behaviours and sleep disturbances. Notably, all of these symptoms typical of an aluminum overload are also typical to two most common neurological disorders of the Western world, one neurodegenerative and the other one neurodevelopmental: Alzheimer's disease and autism. Moreover, there is now sufficient experimental evidence implicating elevated levels of aluminum in both of these disease conditions [2, 4, 6]. In this Hot Topic issue of Current Inorganic Chemistry we have brought together some of the world's experts on the biochemistry of aluminum to consider the potential impacts of aluminum compounds on human health. The issue starts with a discussion of aluminum’s exposome (Exley) and then proceeds to explore how aluminum can impact biological systems through some of its modern compounds, specifically flouroaluminates (Strunecka et al.). In the central part of the issue, Walton challenges the long-term notion that aluminum's role in Alzheimer's disease rests on a myth. Focusing on inflammation, the fourth contribution highlights the ways in which aluminum compounds might promote the onset and progression of neurological diseases in general (Bondy). Blaylock further expands on this concept and shows how not only inflammation, but rather, the interaction between inflammatory mediators and excitotoxins is crucial for the way by which aluminum exerts its toxic actions throughout the central nervous system (CNS). Finally, Yokel demonstrates the many molecular mechanisms by which aluminum might reach the CNS. Importantly, this final evidence clearly negates past notions that aluminum’s accumulation in Alzheimer's is an artifact of passive uptake by dysfunctional neurons. If the focus of this series of articles seems to the reader to be heavily weighted toward the nervous system, then this perception is correct. Aluminum does many things in biological systems, none of them beneficial. But perhaps the most deleterious actions are on CNS structures and function where aluminum impacts seem to be the most egregious at the two ends of the age spectrum: early postnatal life and old age. While in the first case aluminum exposure could precipitate adverse neurodevelopmental outcomes associated with autism [6], in the second case it could lead to one of the most devastating neurodegenerative diseases known to man [4]. The potential for aluminum to do harm can hardly be disputed. The means of remediation from aluminum intoxication are limited at present while the risk of exposure is increasing. It would thus appear that the practical considerations of warnings given by William Gies are now 100 years overdue, “These studies have convinced me that the use in food of aluminum or any other aluminum compound is a dangerous practice” [7]. Perhaps the key to real progress against the rapidly increasing neurological disease burden is to eliminate unnecessary human exposure to aluminum. This issue, we hope, will trigger the long delayed and much needed debate about aluminum in the biosphere and its impact on human health. Finally, we thank all the authors who keenly accepted our invitation to contribute to this issue, as well as the reviewers who invested their valuable time to ensure the high scientific quality of all contributions.