Autophagy in ischemic stroke

Article ID	Journal	Published Year	Pages	File Type
8842182	Progress in Neurobiology	2018	78 Pages	PDF

Abstract

Autophagy is a self-eating cellular catabolic pathway, through which long-lived proteins, damaged organelles and misfolded proteins are degraded and recycled for the maintenance of cellular homeostasis and normal cellular functions. Autophagy plays an important homeostatic role in the regulation of cell survival. Accumulating evidence shows that autophagy is activated in various cell types in the brain such as neurons, glia cells, and brain microvascular cells upon ischemic stroke. However, the exact role and molecular mechanisms of autophagy process that is implicated in ischemic stroke have yet to be elucidated. This review aims to provide a comprehensive view of the regulation of autophagy in neurons, glia cells, and brain microvascular cells in response to ischemia stress. We also review the recent advance on the understanding of the involvement of autophagy in the pathological process during cerebral ischemic preconditioning, perconditioning and postconditioning. We propose a crosstalk between autophagy, necroptosis, and apoptosis that contribute to ischemic stroke. In addition, we discuss the interactions between autophagy and oxidative stress, mitochondrial dysfunction and endoplasmic reticulum stress.

Keywords

AMPK CREB PPAR-γ NF-κB PI3K IL-6 PARP-1 DALYs GFP Nrf2 Aβ mTOR NEMO hsp70 TNFR1 OGD NMDA N-methyl-d-aspartate MCAO PINK1 HIF1 MnSOD UPR ATG eIF2α ATF6 IKK IP3R 3-MA DISC FADD BCCAo NAMPT NMN BFA GRP78 FOXO3 CK2 PKR mTORC1 FXR ZO-1 NLRP3 DAPK RNA-activated protein kinase TIGAR CaMKK TP53-induced glycolysis and apoptosis regulator Jnk1 TRADD LAMP2 TFEB RIP1 DRAM FIP200 XBP1S TSC2 MLKL FUNDC1 PI3KC3 BNIP3L UNC-51-like kinase PGAM5 damage-regulated autophagy modulator NLR family pyrin domain containing 3 TNF-α receptor 1 3-methyladenine AMP-activated protein kinase ULK farnesoid X receptor IκB kinase IRE1α MAPK Mitogen activated protein kinases mTOR complex 1 NOx PTEN-induced putative kinase 1 Small interfering RNA ROS siRNA adenosine 5′-triphosphate ATP amyloid β inositol-requiring enzyme 1α Akt AIF Autophagy middle cerebral artery occlusion bilateral carotid artery occlusion NADPH oxidase interleukin-6 bafilomycin A1 Oxidative stress tumor necrosis factor-α Fas-associated death domain Apoptosis World Health Organization Disability-Adjusted Life Years SOD BBB brain microvascular endothelial cells manganese superoxide dismutase Superoxide dismutase Ischemic stroke endoplasmic reticulum NF-E2-related factor 2 eukaryotic initiation factor 2α apoptosis-inducing factor hypoxia-inducible factor 1 Transcription factor EB phosphoglycerate mutase family member 5 Fas Ligand FasL TNF-α nuclear factor-κB Phosphatidylinositol 3-kinase activating transcription factor 6 TRAIL TNF-related apoptosis-inducing ligand Blood-brain barrier Oxygen-glucose deprivation NF-κB essential modulator Necroptosis NAD Zonula occludens-1 Necrosis nicotinamide adenine dinucleotide nicotinamide phosphoribosyltransferase nicotinamide mononucleotide mammalian target of rapamycin Bcl-2 homology Unfolded protein response cAMP-response element binding protein glucose-regulated protein 78 heat shock protein 70 lysosome-associated membrane protein 2 green fluorescent protein mixed lineage kinase domain-like protein protein kinase B death-associated protein kinase PERK Poly(ADP-ribose) polymerase-1 tuberous sclerosis complex 2 death-inducing signaling complex autophagy-related genes Casein kinase 2 class III phosphatidylinositol 3-kinase WHO Reactive oxygen species Inositol trisphosphate receptor Peroxisome proliferator-activated receptor-γ