oa Editorial [Hot Topic:Cell Metabolism as Therapeutic Target in Human Disease (Executive Guest Editors: Walter Malorni and Rosa Vona)]

Metabolic therapy can be considered as an important new challenge in the cure of different forms of human diseases. Promising and innovative therapeutic strategies are in fact arising from a plethora of experimental and clinical studies. In this Special Issue of Current Pharmaceutical Design, several of these different strategies have been reviewed by leading scientists involved in different areas of investigation either in the field of basic sciences and translational research or in the field of clinical studies on therapeutic intervention. They provide novel insights as concerns metabolic therapy for cardiovascular, neurodegenerative, autoimmune and infectious diseases as well as illustrate new concrete cellular targets of interest for the development of metabolically targeted drugs of possible use in the clinical practice. In particular, Adams and co-authors [1], from the University of Leipzig (Germany), have discussed the role of cachexia that is often associated with severe loss of skeletal muscle mass and a reduced energy metabolism. The maintenance of muscle mass can be generally regarded as a simple balance between protein synthesis and protein degradation. The authors sustain that, in cachexia, all molecular alterations regulating muscle mass and energy production in the skeletal muscle finally leads to a reduction in exercise capacity and provide some suggestion as concerns novel potential targets for the management of this complex metabolic syndrome associated with chronic diseases such as cancer, chronic obstructive pulmonary disease, chronic heart failure, and chronic kidney disease. Nagoshi and co-authors [2], from the Jikei University of Tokyo (Japan), in order to optimize cardiac metabolism in heart failure, suggest a therapeutic approach based on the modification substrate utilization. The derangement of the cardiac energy substrate metabolism plays in fact a key role in the pathogenesis of heart failure. Thus, manipulations that shift energy substrate utilization away from fatty acids toward glucose can improve the cardiac function and slow the progression of heart failure. The authors argue that acceleration of the glucose metabolism, along with the restoration of insulin sensitivity, would be the ideal metabolic therapy for heart failure. Three works of this issue are dedicated to neurodegenerative diseases. The work of Manole and co-workers [3], from the University of Pittsburgh (USA), deals with a novel and intriguing matter of modern medicine: gender differences in cell metabolism. The paper considers different molecular aspects that can be responsible for the observed differences between males and females also analyzing the importance of host factors (sex, age, hormones) and environmental factors (nutrient deprivation, ischemic stress, trauma etc.). In this work, neuronal cell metabolic pathways have been taken into consideration but, conceivably, the gender issue should be expanded to other cell types in a near future. This might lead to an increase of our knowledge on this matter and give raise to innovative gender-“tailored” therapeutic strategies. Viña and co-authors [4], from the University of Valencia (Spain), have discussed the role of oxidative stress in Alzheimer's disease. In fact, it was suggested that several pathogenetic mechanisms involved in the onset and progression of Alzheimer's disease could be related to cell metabolic impairment and to the generation of pro-oxidant species. The authors debate about the need of a putative treatment of Alzheimer's disease with antioxidants. In the same field, but from a different point of view, Smaili and co-workers [5], from the University of Sao Paulo (Brazil), have reviewed the different aspects related to cell loss occurring in neurodegenerative diseases. In particular, these authors described the role of mitochondria in glutamate signaling and brain diseases and provided key information on how these organelles can influence cell fate during glutamate stimulation and calcium signaling. These authors also suggested that autophagy, a key cellular answer to metabolic stress, may function as a protective mechanism that is activated during mitochondrial dysfunction and may protect neuronal cells from injury and degeneration. Hence, autophagy could be considered as a novel target for metabolic therapeutic interventions.....