1. Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases
- Author
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Antonio Cuadrado, Marta Pajares, Ana I. Rojo, Ministerio de Economía y Competitividad (España), and Universidad Autónoma de Madrid
- Subjects
GSSG, glutathione disulfide ,NQO1, NAD(P)H:quinone oxidoreductase 1 ,PrP, prionic protein ,CG islands, cytosine guanine islands ,Review Article ,Biochemistry ,UPR, unfolded protein response ,HD, Huntington's disease ,NRF1 ,lcsh:QH301-705.5 ,GFP, green fluorescent protein ,GSH, glutathione (c-glutamyl-l-cysteinylglycine) ,LIR, LC3 interacting region ,Brain ,ALS, amyotrophic lateral sclerosis ,GSK-3, glycogen synthase kinase-3 ,Cell biology ,NRF2, nuclear factor (erythroid-derived 2)-like 2 ,ASK1, apoptosis-signal-regulating kinase 1 ,lcsh:Medicine (General) ,FOXO, forkhead box ,β-TrCP, β-transducin repeat containing E3 ubiquitin protein ligase ,NF-E2-Related Factor 2 ,ARE, antioxidant response element ,mTOR, mammalian target of rapamycin ,UBA, ubiquitin associated domain ,Protein Aggregation, Pathological ,03 medical and health sciences ,XBP1, X box-binding protein 1 ,PKC, protein kinase C ,γ-GCL, γ -glutamylcysteine synthetase ,Humans ,α-SYN, alpha synuclein ,CJD, Creutzfeldt Jakob disease ,HMOX1, heme oxygenase-1 ,Proteasome ,PI3K, phosphatidyl inositol-3 kinase ,γGS, γ -glutamate cysteine synthetase ,PRX, peroxiredoxin ,030104 developmental biology ,Proteostasis ,Oxidative stress ,Unfolded protein response ,TFEB ,PKA, protein kinase A ,0301 basic medicine ,PDI, protein disulfide isomerase ,Proteome ,Clinical Biochemistry ,Aβ, amyloid beta ,GPX, glutathione peroxidase ,Endoplasmic Reticulum ,CSF, cerebrospinal fluid ,PD, Parkinson's disease ,GST, glutathione S-transferase ,TFEB, transcription factor EB ,ASK1 ,SOD1, Cu/Zn-superoxide dismutase 1 ,MAPKs, mitogen-activated protein kinases ,SFN, sulforaphane ,Genetics ,PS1, presenilin 1 ,lcsh:R5-920 ,MPTP, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine ,Neurodegenerative diseases ,NRF1, nuclear factor (erythroid-derived 2)-like 1 ,GR, GSR, glutathione reductase ,ChIP, chromatin immunoprecipitation ,GCLM, glutamate-cysteine ligase modulatory subunit ,IRE1, inositol-requiring kinase 1 ,JNK, c-Jun N-terminal kinase ,AD, Alzheimer's disease ,DMF, dimethyl fumarate ,Proteasome Endopeptidase Complex ,XBP1 ,TAK1, TGF-β-activated kinase 1 ,γGT, γ -glutamyl transpeptidase ,Protein degradation ,Biology ,ER, endoplasmic reticulum ,ROS, reactive oxygen species ,UPS, ubiquitin proteasome system ,APP, amyloid precursor protein ,Autophagy ,D3T, 1,2-dithiole-3-thione ,Transcription factor ,MEF, mouse embryonic fibroblasts ,Htt, huntingtin ,Ubiquitin ,Organic Chemistry ,ERO1, sulfhydryl oxidase endoplasmic oxidoreductin 1 ,AMPK, AMP-activated protein kinase ,lcsh:Biology (General) ,ATF-6, activating transcription factor 6 ,PERK, pancreatic ER eIF2α kinase ,GLT-1, glutamate transporter 1 ,GCLC, glutamate-cysteine ligase catalytic subunit ,KEAP1, kelch-like ECH-associated protein 1 - Abstract
Neurodegenerative diseases are linked to the accumulation of specific protein aggregates, suggesting an intimate connection between injured brain and loss of proteostasis. Proteostasis refers to all the processes by which cells control the abundance and folding of the proteome thanks to a wide network that integrates the regulation of signaling pathways, gene expression and protein degradation systems. This review attempts to summarize the most relevant findings about the transcriptional modulation of proteostasis exerted by the transcription factor NRF2 (nuclear factor (erythroid-derived 2)-like 2). NRF2 has been classically considered as the master regulator of the antioxidant cell response, although it is currently emerging as a key component of the transduction machinery to maintain proteostasis. As we will discuss, NRF2 could be envisioned as a hub that compiles emergency signals derived from misfolded protein accumulation in order to build a coordinated and perdurable transcriptional response. This is achieved by functions of NRF2 related to the control of genes involved in the maintenance of the endoplasmic reticulum physiology, the proteasome and autophagy., This paper was funded by grant SAF2016-76520-R of the Spanish Ministry of Economy and Competitiveness. MP is recipient of a FPU fellowship of Autonomous University of Madrid.
- Published
- 2017
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