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Molecular Neurodegeneration

, 12:42

First Online: 25 May 2017Received: 07 December 2016Accepted: 17 May 2017DOI: 10.1186-s13024-017-0183-y

Cite this article as: Sprenkle, N.T., Sims, S.G., Sánchez, C.L. et al. Mol Neurodegeneration 2017 12: 42. doi:10.1186-s13024-017-0183-y

Abstract

Persistent endoplasmic reticulum ER stress is thought to drive the pathology of many chronic disorders due to its potential to elicit aberrant inflammatory signaling and facilitate cell death. In neurodegenerative diseases, the accumulation of misfolded proteins and concomitant induction of ER stress in neurons contributes to neuronal dysfunction. In addition, ER stress responses induced in the surrounding neuroglia may promote disease progression by coordinating damaging inflammatory responses, which help fuel a neurotoxic milieu. Nevertheless, there still remains a gap in knowledge regarding the cell-specific mechanisms by which ER stress mediates neuroinflammation. In this review, we will discuss recently uncovered inflammatory pathways linked to the ER stress response. Moreover, we will summarize the present literature delineating how ER stress is generated in Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis, and highlight how ER stress and neuroinflammation intersect mechanistically within the central nervous system. The mechanisms by which stress-induced inflammation contributes to the pathogenesis and progression of neurodegenerative diseases remain poorly understood. Further examination of this interplay could present unappreciated insights into the development of neurodegenerative diseases, and reveal new therapeutic targets.

KeywordsEndoplasmic reticulum stress Unfolded protein response Neuroinflammation Neurodegeneration AbbreviationsADAlzheimer’s disease

ALSAmyotrophic Lateral Sclerosis

AP-1Activator protein 1

APPAβ precursor protien

ASK1Apoptosis signal-regulating kinase 1

ATFActivating transcription factor

AβAmyloid-β

BBBBlood brain barrier

BiPbinding immunoglobulin protein

bZIPbasic leucine zipper

CHOPCCAAT-enhancer-binding protein homologous protein

CNSCentral nervous system

DAMPdanger-associated molecular patterns

eIF2αeukaryotic translation initiation factor 2α

EREndoplasmic reticulum

ERADER-associated degradation

Ero1αER oxidoreductase α

FADFamilial Alzheimer’s disease

GADD34Growth arrest and DNA damage-inducible protein 34

GCN2General control non-derepressible 2

GRPGlucose-regulated protein

GSK-3Glycogen synthase kinase 3

HERVhuman endogenous retrovirus

HLAHuman leukocyte antigen

IFN-γInterferon-γ

IKKIκB kinase

ILInterleukin

IRE-1αInositol-requiring 1α

IκBinhibitors of κB;

JAK1Januse kinase 1

JNKc-Jun N-terminal kinase

Keap1Kelch-like ECH-associated protein 1

LRRK2Leucine-rich repeat kinase 2

MAPKMitogen activated protein kinase

MEFMouse embryonic fibroblasts

MSMultiple Sclerosis

NFTNeurofibrillary tangle

NF-κBNuclear factor kappa-light-chain-enhancer of activated B cells

NOD1-2Nucleotide-binding oligomerization domain 1-2

Nrf-2Nuclear factor-like 2

PAMPpathogen-associated molecular patterns

PDParkinson’s disease

PDIProtein disulphide isomerase

PERKDouble-stranded RNA dependent protein kinase-like ER kinase

PKRDouble stranded RNA-dependent kinase

PPIProtein phosphatase 1

PSPresenilin

RIDDRegulated IRE1-dependent decay

RIPK2Receptor-interacting serine-threonine-protein kinase 2

RNaseEndoribonuclease

RNSReactive nitrogen species

ROSReactive oxygen species

SRPSignal-recognition particle

STATSignal transducers and activators of transcription

sXBP1Spliced x-box-binding protein 1

TNF-αTumor-necrosis factor-α

TRAF2TNF-α-receptor-associated factor 2

UPRUnfolded protein response

WTWild-type

XBP1X-box-binding protein 1





Autor: Neil T. Sprenkle - Savannah G. Sims - Cristina L. Sánchez - Gordon P. Meares

Fuente: https://link.springer.com/







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