Autophagy, endoplasmic reticulum stress and the unfolded protein response in intracerebral hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is a subtype of stroke that is followed by primary and secondary brain injury. As a result of the injury, cell metabolism is disrupted and a series of stress responses are activated, such as endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to the re-establishment of cell homeostasis or cell death. As an important mechanism of cell homeostasis, autophagy has been widely studied, and the associations between autophagy, ER stress, and the UPR have also been demonstrated. Whether these mechanisms are beneficial or detrimental remains a matter of controversy, but there is no doubt as to their vital functions. An understanding of the mechanisms of injury and recovery after ICH is crucial to develop therapeutic strategies. In this review, we summarize the related studies and highlight the roles of autophagy, ER stress, and the UPR in disease, especially in ICH. We also provide an overview of therapeutic approaches that target autophagy, and we discuss the prospects for modulating autophagy, ER stress, and UPR mechanisms in ICH therapy.

Long noncoding ribonucleic acid NKILA induces the endoplasmic reticulum stress/autophagy pathway and inhibits the nuclear factor‐k‐gene binding pathway in rats after intracerebral hemorrhage

“…The pairwise comparisons were made using the least significant difference post hoc test after one-way ANOVA; *P < 0. therapeutic strategies exist for ICH (Balami & Buchan, 2012). Alleviation of brain injury and improvement of neuronal survival have been proposed as therapeutic objectives (Niu et al, 2017), and lncRNA, ERS, as well as autophagy are involved (X. Zhang et al, 2014;Yu, Cao, Ran, & Wang, 2017).…”

A Role for Endoplasmic Reticulum Stress in Intracerebral Hemorrhage

“…ICH disrupts cell metabolism and it is shown to activate a series of stress responses including ER stress [79]. On the other hand, ER dysfunction caused by protein misfolding and oxidative stress has led to acute central nervous system damage [80,81].…”

Cordycepin‐induced unfolded protein response‐dependent cell death, and AKT/MAPK‐mediated drug resistance in mouse testicular tumor cells

“…ER stress then subsequently triggers the unfolded protein response (UPR), a complex intracellular signal transduction pathway, to increase the protein folding capacity and decrease unfolded protein load . In response to the environmental and genetic stresses, the UPR and autophagy are important mechanisms involved in the regulation of cellular stress responses, and both of them are interconnected . Many studies have focused on the UPR and autophagy as novel therapeutic targets for cancers because of the difference of metabolic mechanism and dependence on stress responses between normal and malignant cells .…”

“…[8][9][10] In response to the environmental and genetic stresses, the UPR and autophagy are important mechanisms involved in the regulation of cellular stress responses, and both of them are interconnected. 10,11 Many studies have focused on the UPR and autophagy as novel therapeutic targets for cancers because of the difference of metabolic mechanism and dependence on stress responses between normal and malignant cells. [12][13][14] ER stress induces UPR by activating three master sensors located in the ER membrane: double-stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 (IRE1).…”