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Ischemic Stroke-Induced Endoplasmic Reticulum Stress

  • Namrata RastogiEmail author
  • Vikas Kumar Srivastava
Chapter

Abstract

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.

Keywords

Cerebral ischemia IR injury ER stress Autophagy and microRNAs 

Abbreviations

ASK1

Apoptosis signal-regulating kinase 1

ATF/CREB

Activating transcription factor/cyclic AMP response element binding protein

ATF4

Activating transcription factor 4

ATF6

Activating transcription factor 6

bcl-2

B-cell lymphoma-2

BIP

Binding immunoglobulin protein

CHOP

CCAAT/enhancer binding protein homologous protein

COX-2

Cyclooxygenase-2

CRE

cAMP-response element

CREB

cAMP-response element binding factor

ER

Endoplasmic reticulum

ERSE

ER stress-response elements

GADD34

Growth arrest and DNA damage-inducible gene/protein 34

GRP78

Glucose-regulated protein 78

IR

Ischemia/reperfusion

IRE1

Inositol-requiring enzyme-1

JNK

c-Jun N-terminal kinase

MCAO

middle cerebral artery occlusion

MAPKs

Mitogen-activated protein kinases

miR

microRNA

nNOS

Neuronal NOS

NOS

Nitric oxide synthase

OGD

Oxygen and glucose deprivation

p38 MAPK

p38 mitogen-activated protein kinase

PERK

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

PSI

Protein synthesis inhibition

TRAF2

Tumor necrosis factor receptor-associated factor 2

UPR

Unfolded protein response

XBP1

X-box-binding protein 1

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Copyright information

© 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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