Editorial [Hot Topic: Mechanisms of Cell Death: Biomedical Implications (Executive Editor: E. Ottaviani)]

Cell death is a basic element occurring not only in the normal organism functioning but also in many forms of aging and pathologies. The reviews here collected focus on the important role that the different types of cell death, or the interplay among them, can play in many forms of aging and pathologies discussing also how cell death may be exploited for therapeutic purposes in human diseases. McLean et al. focus on the most recent and important advances in understanding how a wide range of viruses manipulate the survival and death of their hosts. Viruses appear to be able to intervene at all steps of eukaryotic cell death, both to prevent death and ultimately to provoke it. By unraveling the specific details surrounding virus-host interactions, novel therapeutic targets, and aid in improved vaccine design, as well as a clearer insight into the complex machinery of eukaryotic cell death have been reported. Vannini et al. describe some functional changes encountered by endothelial cells during the aging process that predispose these cells to apoptosis. It is clear how inflammation and redox imbalance are the main features involved in this death process thus they propose a dietary use of safe anti-oxidants as NAC as suitable tool in the prevention of endothelium aging and subsequently in the prevention of cancer and cardiovascular disease. Salvioli et al. discuss how cell death phenomena are modulated during aging and what is their possible role in the aging process. Since the “decisional process” that leads the cell to death is very complex, the systems biology approach has been shown to be effective in giving structure and increasing understanding of both apoptosis and cell senescence, thus offering a promising tool to disentangle the inherent complexity of the biochemical decision processes that lead to cell death or survival. Cossarizza focuses on the relationship between apoptosis and HIV. The infection with HIV is characterized by the activation of several molecular and cellular mechanisms that the organism triggers to cope with the virus and eliminate dangerous, infected cells. The virus can play different parts, because immune cells devoted to its control have to be killed, but such cells are often required for viral replication. In such a complex equation, the action of different antiretroviral drugs and cytokines can significantly influence apoptosis. Matarrese et al. in their review summarize the findings reported in literature on a phagic process that appears to be related to self-cannibalism: the xeno-cannibalism. This was described as the ability of certain cells, e.g. metastatic cells, to cannibalize their siblings as well as cells from the immune system. Furthermore, they suggest a pathogenetic role for cannibalic behavior in human pathology and point at this surprising cellular aggressiveness as an innovative pharmacological target in the clinical management of metastatic disease. Giovannetti et al. consider some key facts on the relationship of lymphopenia to autoreactivity, the mechanisms controlling positive and negative selection in the thymus, the role of apoptosis in selected primary immunodeficiency states and in systemic and organ-specific autoimmunity, with examples from human diseases and their animal models. Rovere-Querini et al. report recent developments on the control of apoptosis induction and execution, discussing how cell death may be exploited for therapeutic purposes. The links among cell death, persisting inflammation, stem cell recruitment and activation in experimental models of complex human diseases are also analyzed. Malorni et al. review the recent developments in the comprehension of the role played by type 2 transglutaminase (TG2) in eukaryotic cells, focusing on the role exerted by TG2 on mitochondrial physiology and on the regulation of cell death pathways at the basis of neurodegenerative diseases....