Hyperhomocysteinemia (hHCy) is a recognized comorbid risk factor of human brain stroke. We overview here the recent data on the homocysteine (Hcy) metabolism and on the genetic and metabolic causes of hHCy‐related neuropathologies. In context of our results which detected an increased oxidative stress in hyperhomocysteinemic rats, we discuss here the role of free radicals in this disorder. Brain ischemia‐reperfusion causes delayed neuronal death. Ischemic tolerance evoked by preconditioning (IPC) represents a phenomenon of central nervous system (CNS) adaptation to any subsequent ischemia. The paper describes changes in the mitogen‐activated protein kinases (MAPKs) protein pathways, and apoptotic markers were used to follow the degeneration process. Our studies provide evidence for the interplay and tight integration between extracellular signal‐regulated kinase (ERK) and p38 MAPKs signaling mechanisms in response to the hHCy and also in association with brain ischemia/IPC challenge. Recognition of the effects of risk factors in the ischemic tolerance would lead to improved therapeutics, especially the brain tissue.
Part of the book: Ischemic Stroke
Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy (mitochondrial autophagy) and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications (PTMs). The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less adenosine triphosphate (ATP), release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability throughout aging in myocardial cells. Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Assume all together, dysfunctional proteostasis can play a causative role in aging and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders.
Part of the book: Mitochondrial Diseases