title: Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases.
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.
authors.affiliation: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC, Madrid, Spain; Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pajares
authors.affiliation: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC, Madrid, Spain; Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cuadrado
authors.affiliation: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Investigación Sanitaria La Paz (IdiPaz), Instituto de Investigaciones Biomédicas Alberto Sols UAM-CSIC, Madrid, Spain; Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain. Electronic address: airojo@iib.uam.es.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Rojo
mesh_terms: D001343:Autophagy / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D066263:Protein Aggregation, Pathological; D020543:Proteome / Q000235:genetics*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D020543:Proteome; D046988:Proteasome Endopeptidase Complex
keywords: Autophagy; Neurodegenerative diseases; Oxidative stress; Proteasome; Ubiquitin; Unfolded protein response