Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Mitochondrial dysfunction : common final pathway in brain aging and Alzheimer's disease : therapeutic aspects

As a fully differentiated organ, our brain is very sensitive to cumulative oxidative damage of proteins, lipids, and DNA occurring during normal aging because of its high energy metabolism and the relative low activity of antioxidative defense mechanisms. As a major consequence, perturbations of energy metabolism including mitochondrial dysfunction, alterations of signaling mechanisms and of gene expression culminate in functional deficits. With the increasing average life span of humans, age-related cognitive disorders such as Alzheimer's disease (AD) are a major health concern in our society. Age-related mitochondrial dysfunction underlies most neurodegenerative diseases, where it is potentiated by disease-specific factors. AD is characterized by two major histopathological hallmarks, initially intracellular and with the progression of the disease extracellular accumulation of oligomeric and fibrillar beta-amyloid peptides and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. In this review, we focus on findings in AD animal and cell models indicating that these histopathological alterations induce functional deficits of the respiratory chain complexes and therefore consecutively result in mitochondrial dysfunction and oxidative stress. These parameters lead synergistically with the alterations of the brain aging process to typical signs of neurodegeneration in the later state of the disease, including synaptic dysfunction, loss of synapses and neurites, and finally neuronal loss. We suggest that mitochondrial protection and subsequent reduction of oxidative stress are important targets for prevention and long-term treatment of early stages of AD

Evolutionary Specialization of the Tongue in Vertebrates: Structure and Function

A conspicuous feature of extant tetrapods is a movable tongue that plays a role in food uptake, mastication, and swallowing. The tongue is a muscle mass covered by a mucosal sheath, but the tongues of amphibians, reptiles, birds, and mammals are diverse in general morphology and function. For example, in frogs and toads, a component of the musculus genioglossus serves as an intrinsic tongue muscle, with the anterior part of the tongue attached to the floor of the oral cavity. Nevertheless, these features of the tongue have allowed Anurans to diversify and disperse worldwide. On the other hand, the salamander tongue is connected to the oral cavity by a root with a cartilage or a bony skeleton, and it is mainly comprised of projection and retractor muscles. In this respect, the salamander tongue seems more similar to that of reptiles and mammals than to those of frogs and toads. The morphology and function of the tongues of some reptiles, such as chameleons, and some mammals, such as nectar-feeding bats, are examples of extreme specialization. Finally, the tongue has become almost vestigial in a few species of anurans, turtles, and birds. This review summarizes and discusses many specializations of tongue form and function among tetrapods