Neurochemistry International 62 (2013) 521
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Oxidative stress and neurodegeneration
When the concept of a Special Issue entitled ‘‘Oxidative Stress and Neurodegeneration’’ was ﬁrst advanced at the Editorial Board Meeting of Neurochemistry International in Athens in 2011 nobody imagined it would grow to the present volume. Indeed what stands out from this focused issue of 29 manuscripts is not only their diversity in terms of the neuroscience topics addressed, but also the wide distribution of contributing laboratories internationally. In hindsight this should not have been a total surprise to the Editors as there are more than 13,000 entries in PubMed if you pair the search terms oxidative stress and brain, and oxidative stress and its contribution to brain pathologies remain a huge area of study pertinent to all branches of neuroscience. In this Special Issue on ‘‘Oxidative Stress and Neurodegeneration’’, we bring together contributions from leaders in neural oxidative stress research to provide an up-to-date account of how and why oxidative changes occur during neurodegeneration, their contribution to the disease process and ultimately how oxidative stress may be targeted using therapeutic treatment strategies. The science covered ranges from systems biology and gene proﬁling through work in cultured cells to more physiological studies and drug development. This broad coverage highlights major advances in methodologies and the success of translational research in this exciting ﬁeld of neuroscience. The diversity of this volume in some way reﬂects the unmet clinical need in that while oxidative stress is recognized as a key injury mechanism there are no real therapies to prevent its destructive downstream consequences on the brain. This unmet need at least partially explains the consumption by the public at large of huge amounts of complementary medicines and manuscripts from Steele et al. and Singh et al. describing protective effects of plant extracts are pertinent to this topic. From a drug development and ‘‘bench to bedside’’ perspective, an elegant example is the article by Greenough et al. who discuss the logic behind the development of metal binding compounds designed to cross the blood brain barrier and to restore metal homeostasis as potential therapeutics for Alzheimer’s disease (AD). In this context Cu, Al, Fe, Mn and Hg continue to attract attention for their toxicities and hence as therapeutic modalities (see Scheiber et al., Bolognin et al., and Aschner et al.). Other articles contained herein cover protective effects in the oxidative milieu of curcumin (Eckert et al.), hydrogen sulﬁde (Liu et al.), guanosine (Albrecht et al.), D-bhydroxybutyrate (Cheng et al.) and docosahexaenoic acid (Cieslik et al.) demonstrating a diversity of therapeutic approaches that parallels the international distribution of the participating laboratories.
0197-0186/$ - see front matter Ó 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.neuint.2013.03.006
Across the ﬁeld of oxidative injury the broad-based search for mechanistic insights, especially the elucidation and prioritization of injury mechanisms, continues apace. Such work might be more focused on individual neuropathologies such as Parkinson’s disease where a systems biology approach of the genes and pathways represents one strategy (Funke et al.) or alternatively gene expression proﬁling in neuronal (Yap et al.) or animal models (Czapski et al.). The roles of reactive oxygen and nitrogen species in neuronal injury as a consequence of the malfunction of the oxidative respiratory chain in mitochondria remain a topic a great interest. Here complex I continues to attract huge attention (see Madathil et al., Allen et al. and Polster). This series of articles highlights the importance of oxidative stress as a major contributing factor in a range of brain pathologies. Destructive effects of oxidative stress are likely to be exacerbated by raised cellular calcium (Goodwin et al.), cytoplasmic oxidases (Manzanero et al.), excitotoxicity (Chen et al.), elevated synthesis of L-glutamine (Skowronska et al.), dysfunction of anti-oxidant systems (Conrad et al.), discoordinate energy supply (RodriguezRodriguez et al.), inappropriate dehydrogenase activity (AdamVizi and Tretter), DNA damage (Smith et al.), protein aggregates (Wilkaniec et al.) and diabetic complications (Lind et al.). One cannot help but ponder the implications here for society with the growing incidence of neurodegenerative conditions. Neuroinﬂammation continues to grow almost exponentially as a topic of interest internationally and is attracting attention as a drug target in a various neuropathologies, including ischemic injury, WernickeKorsakoff syndrome (Hazell et al.) and Parkinsonism (Taylor et al.), as a ‘‘co-conspirator’’ sharing many molecular commonalities with oxidative stress. The coverage offered here will be of broad interest to workers in the ﬁeld be they teachers, students, academic or commercial researchers. Not only do the mechanistic insights indicate seminal areas that require detailed investigation, but the contemporary reviews allow neuroscientists internationally to conveniently grasp the status quo and emerging concepts on oxidative stress in neurodegeneration. There is much food for thought here – enjoy! Anthony White Carsten Culmsee Philip Beart