Cell death pathways in injured cardiomyocytes and neurons

Cell death pathways in injured cardiomyocytes and neurons refer to the diverse set of regulated molecular mechanisms that lead to the loss of these critical post-mitotic cells following pathological insults such as ischemia-reperfusion or oxidative stress (Galluzzi et al., 2018, Nature Reviews Molecular Cell Biology). These pathways include apoptosis, characterized by caspase activation; necroptosis, a programmed form of necrosis mediated by RIPK1/RIPK3/MLKL; and ferroptosis, driven by iron-dependent lipid peroxidation (Del Re et al., 2019, Circ Res). In the heart, the activation of these pathways during myocardial infarction leads to irreversible loss of myocardium and subsequent heart failure (Teringova & Tousek, 2017, Int J Mol Sci). In the brain, similar mechanisms drive neuronal loss in acute stroke and chronic neurodegenerative conditions (Fricker et al., 2018, Physiol Rev). While these pathways offer multiple therapeutic targets, such as RIP kinases or mitochondrial transition pores, the significant crosstalk between them often necessitates combinatorial approaches to effectively preserve tissue function (Kuwano et al., 2018, JCI Insight).

Other names

Regulated cell death (RCD)Programmed cell death (PCD)Ischemia-reperfusion injury pathwaysMyocardial and neuronal cell death mechanisms

Inhibition of regulated cell death executioners, such as caspases, RIP kinases, or lipid peroxidases, to prevent the loss of post-mitotic cells in the heart and brain.