ABSTRACT
Cardiac aging, particularly cardiac cell senescence, is a natural process that occurs as we age. Heart function gradually declines in old age, leading to continuous heart failure, even in people without a prior history of heart disease. To address this issue and improve cardiac cell function, it is crucial to investigate the molecular mechanisms underlying cardiac senescence. This review summarizes the main mechanisms and key proteins involved in cardiac cell senescence. This review further discusses the molecular modulators of cellular senescence in aging hearts. Furthermore, the discussion will encompass comprehensive descriptions of the key drugs, modes of action and potential targets for intervention in cardiac senescence. By offering a fresh perspective and comprehensive insights into the molecular mechanisms of cardiac senescence, this review seeks to provide a fresh perspective and important theoretical foundations for the development of drugs targeting this condition.
ABSTRACT
Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.
Subject(s)
Cardiovascular Diseases , Ferroptosis , Trace Elements , Humans , IronABSTRACT
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with ~50 million people experiencing TBI each year. Ferroptosis, a form of regulated cell death triggered by iron ion-catalyzed and reactive oxygen species-induced lipid peroxidation, has been identified as a potential contributor to traumatic central nervous system conditions, suggesting its involvement in the pathogenesis of TBI. Alterations in iron metabolism play a crucial role in secondary injury following TBI. This study aimed to explore the role of ferroptosis in TBI, focusing on iron metabolism disorders, lipid metabolism disorders and the regulatory axis of system Xc-/glutathione/glutathione peroxidase 4 in TBI. Additionally, we examined the involvement of ferroptosis in the chronic TBI stage. Based on these findings, we discuss potential therapeutic interventions targeting ferroptosis after TBI. In conclusion, this review provides novel insights into the pathology of TBI and proposes potential therapeutic targets.
ABSTRACT
Globally, ischemic stroke causes millions of deaths per year. The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and reperfusion-related neuronal death in the infarct region. In the infarct region, cell injuries follow either the regulated pathway involving precise signaling cascades, such as apoptosis and autophagy, or the nonregulated pathway, which is uncontrolled by any molecularly defined effector mechanisms such as necrosis. However, numerous studies have recently found that a certain type of necrosis can be regulated and potentially modified by drugs and is nonapoptotic; this type of necrosis is referred to as regulated necrosis. Depending on the signaling pathway, various elements of regulated necrosis contribute to the development of ischemic stroke, such as necroptosis, pyroptosis, ferroptosis, pathanatos, mitochondrial permeability transition pore-mediated necrosis and oncosis. In this review, we aim to summarize the underlying molecular mechanisms of regulated necrosis in ischemic stroke and explore the crosstalk and interplay among the diverse types of regulated necrosis. We believe that targeting these regulated necrosis pathways both pharmacologically and genetically in ischemia-induced neuronal death and protection could be an efficient strategy to increase neuronal survival and regeneration in ischemic stroke.
ABSTRACT
Cardiovascular diseases (CVDs) have been recognized as the leading cause of premature mortality and morbidity worldwide despite significant advances in therapeutics. Inflammation is a key factor in CVD progression. Once stress stimulates cells, they release cellular compartments known as damage-associated molecular patterns (DAMPs). Mitochondria can release mitochondrial DAMPs (mtDAMPs) to initiate an immune response when stimulated with cellular stress. Investigating the molecular mechanisms underlying the DAMPs that regulate CVD progression is crucial for improving CVDs. Herein, we discuss the composition and mechanism of DAMPs, the significance of mtDAMPs in cellular inflammation, the presence of mtDAMPs in different types of cells, and the main signaling pathways associated with mtDAMPs. Based on this, we determined the role of DAMPs in CVDs and the effects of mtDAMP intervention on CVD progression. By offering a fresh perspective and comprehensive insights into the molecular mechanisms of DAMPs, this review seeks to provide important theoretical foundations for developing drugs targeting CVDs.
