Ischemic Stroke-Induced Endoplasmic Reticulum Stress

  • Namrata RastogiEmail author
  • Vikas Kumar Srivastava


Endoplasmic reticulum (ER) stress is a complex cellular mechanism that is induced by the accumulation of misfolded proteins under various stress stimuli. ER stress is implicated in various pathological conditions, including cerebral ischemia. In cerebral ischemia, ER stress is presumed to be an early event and pro-survival. However, its precise involvement in ischemia/reperfusion (IR) injury is still contentious and under investigation. Mechanistically, ER stress and its associated unfolded protein response is presumed to be a defensive mechanism, which, when it becomes chronic, has fatal effects on neuronal survival and outcomes of stroke patients. Recent investigations have presented interesting contributions of autophagy to cerebral ER stress. As an innate process, autophagy is a defensive process for neuronal cell survival, but when triggered by chronic ER stress, it becomes destructive and induces cell death. Moreover, other factors, such as small non-coding microRNAs (miRs), have also been shown to regulate both of these processes through their gene expression regulatory properties. However, it is still very important to understand the interrelationship between ER stress and autophagy in IR injury following cerebral stroke so as to define its therapeutic significance. Furthermore, we need to approach combined therapies using ER stress and autophagy inhibitors with the intent to improve current treatments for cerebral stroke.


Cerebral ischemia IR injury ER stress Autophagy and microRNAs 



Apoptosis signal-regulating kinase 1


Activating transcription factor/cyclic AMP response element binding protein


Activating transcription factor 4


Activating transcription factor 6


B-cell lymphoma-2


Binding immunoglobulin protein


CCAAT/enhancer binding protein homologous protein




cAMP-response element


cAMP-response element binding factor


Endoplasmic reticulum


ER stress-response elements


Growth arrest and DNA damage-inducible gene/protein 34


Glucose-regulated protein 78




Inositol-requiring enzyme-1


c-Jun N-terminal kinase


middle cerebral artery occlusion


Mitogen-activated protein kinases




Neuronal NOS


Nitric oxide synthase


Oxygen and glucose deprivation

p38 MAPK

p38 mitogen-activated protein kinase


Double-stranded RNA-dependent protein kinase-like ER kinase


Protein synthesis inhibition


Tumor necrosis factor receptor-associated factor 2


Unfolded protein response


X-box-binding protein 1


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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Hematology Department, Division of Cancer and Genetics, School of MedicineCardiff UniversityCardiffUK
  2. 2.Division of Environmental ToxicityCSIR-Indian Institute of Toxicological ResearchLucknowIndia

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