The relevance of pathophysiological alterations in redox signaling of 4-hydroxynonenal for pharmacological therapies of major stress-associated diseases

Modern analytical methods combined with the modern concepts of redox signaling revealed 4-hydroxy-2-nonenal (4-HNE) as particular growth regulating factor involved in redox signaling under physiological and pathophysiological circumstances. In this review current knowledge of the relevance of 4-HNE as “the second messenger of reactive oxygen species” (ROS) in redox signaling of representative major stress-associated diseases is briefly summarized. The findings presented allow for 4-HNE to be considered not only as second messenger of ROS, but also as one of fundamental factors of the stress- and age-associated diseases. While standard, even modern concepts of molecular medicine and respective therapies in majority of these diseases target mostly the disease-specific symptoms. 4-HNE, especially its protein adducts, might appear to be the bioactive markers that would allow better monitoring of specific pathophysiological processes reflecting their complexity. Eventually that could help development of advanced integrative medicine approach for patients and the diseases they suffer from on the personalized basis implementing biomedical remedies that would optimize beneficial effects of ROS and 4-HNE to prevent the onset and progression of the illness, perhaps even providing the real cure. [Display omitted] •4-HNE plays important roles in pathophysiology of major stress-associated diseases.•4-HNE affects signaling pathways in concentration- and cell-type dependent manner.•Pathophysiological effects of 4-HNE mostly involve relevant protein modifications.•Current pharmacological designs are unaware of pathophysiological roles of 4-HNE.•Integrative biomedicine should tackle the pathophysiology of 4-HNE signaling.