Chopping Out CHOP Chops the Fate of Neurons

Abstract

In Basic Science Commentary We all seem to know that "seizures beget seizures, " but do we really know why? Seizure-induced neuronal cell death may play a contributing role under certain circumstances (1, 2), and a variety of endogenous neuroprotective mechanisms are in place to limit neuronal injury (3-5). Neuronal cell loss in epilepsy is not straightforward and can depend upon spatial patterns, cell types, and timing of pathways that can either promote or reduce injury (3). Prolonged seizures are thought to induce excessive glutamate receptor activation, leading to the disruption of intracellular calcium homeostasis, oxidative stress, DNA damage, and dysfunction of intracellular organelles-among which, the unfolded protein response and associated endoplasmic reticulum stress might play a crucial role. This response can trigger apoptosis through the protooncogene CCAAT/enhancer-binding protein homologous protein (CHOP), which is a transcription factor induced by all three differing pathways triggered by the unfolded protein response (6). The precise role of CHOP in cell death pathways has been highly controversial. Based on findings that CHOPenhances neuronal cell death in models of neurodegeneration

Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation

“…Tissue protection is likely a function of cellular stress adaptation pathways, which allow cells to survive noxious states such as increased free radicals and accumulation of unfolded proteins (Figueiredo et al, 2013; Larsen et al, 2010). When these adaptation pathways are overwhelmed, cells can undergo apoptotic cell death (Boison, 2013; Tabas and Ron, 2011). Thus, one important determinant of host tolerance may be related to the ability of cellular adaptation programs to tolerate noxious states found in infections (Medzhitov et al, 2012).…”