title: Neuroprotection requires the functions of the RNA-binding protein HuR.
abstract: Alterations in the functions of neuronal RNA-binding proteins (RBPs) can contribute to neurodegenerative diseases. However, neurons also express a set of widely distributed RBPs that may have developed specialized functions. Here, we show that the ubiquitous member of the otherwise neuronal Elavl/Hu family of RNA-binding proteins, Elavl1/HuR, has a neuroprotective role. Mice engineered to lack exclusively HuR in the hippocampal neurons of the central nervous system (CNS), maintain physiologic levels of neuronal Elavls and develop a partially diminished seizure response following strong glutamatergic excitation; however, they display an exacerbated neurodegenerative response subsequent to the initial excitotoxic event. This response was phenocopied in hippocampal cells devoid of ionotropic glutamate receptors in which the loss of HuR results in enhanced mitochondrial dysfunction, oxidative damage and programmed necrosis solely after glutamate challenge. The molecular dissection of HuR and nElavl mRNA targets revealed the existence of a HuR-restricted posttranscriptional regulon that failed in HuR-deficient neurons and is involved in cellular energetics and oxidation defense. Thus, HuR acts as a specialized controller of oxidative metabolism in neurons to confer protection from neurodegeneration.
authors.affiliation: Biomedical Sciences Research Centre 'Alexander Fleming', 16672 Vari, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Skliris
authors.affiliation: Biomedical Sciences Research Centre 'Alexander Fleming', 16672 Vari, Greece.
authors.forename: O
authors.initials: O
authors.lastname: Papadaki
authors.affiliation: Biomedical Sciences Research Centre 'Alexander Fleming', 16672 Vari, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Kafasla
authors.affiliation: Biomedical Sciences Research Centre 'Alexander Fleming', 16672 Vari, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Karakasiliotis
authors.affiliation: Biomedical Sciences Research Centre 'Alexander Fleming', 16672 Vari, Greece.
authors.forename: O
authors.initials: O
authors.lastname: Hazapis
authors.affiliation: Biomedical Sciences Research Centre 'Alexander Fleming', 16672 Vari, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Reczko
authors.affiliation: Biomedical Sciences Research Centre 'Alexander Fleming', 16672 Vari, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Grammenoudi
authors.affiliation: Centre for Brain Research, Medical University of Vienna, A109 Vienna, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Biomedical Sciences Research Centre 'Alexander Fleming', 16672 Vari, Greece.
authors.forename: D L
authors.initials: DL
authors.lastname: Kontoyiannis
mesh_terms: D000818:Animals; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D012640:Seizures / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000067780:ELAV-Like Protein 1; C000593997:Elavl1 protein, mouse; D009419:Nerve Tissue Proteins; D018698:Glutamic Acid