title: Neuroprotective role of the basic leucine zipper transcription factor NFIL3 in models of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons. Here we show that the basic leucine zipper transcription factor NFIL3 (also called E4BP4) confers neuroprotection in models of ALS. NFIL3 is up-regulated in primary neurons challenged with neurotoxic insults and in a mouse model of ALS. Overexpression of NFIL3 attenuates excitotoxic neuronal damage and protects neurons against neurodegeneration in a cell-based ALS model. Conversely, reduction of NFIL3 exacerbates neuronal demise in adverse conditions. Transgenic neuronal expression of NFIL3 in ALS mice delays disease onset and attenuates motor axon and neuron degeneration. These results suggest that NFIL3 plays a neuroprotective role in neurons and constitutes a potential therapeutic target for neurodegeneration.
authors.affiliation: From the Molecular Genetics Research Laboratory, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: So-ichi
authors.initials: S
authors.lastname: Tamai
authors.forename: Keisuke
authors.initials: K
authors.lastname: Imaizumi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kurabayashi
authors.forename: Minh Dang
authors.initials: MD
authors.lastname: Nguyen
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inoue
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukada
authors.forename: Kamon
authors.initials: K
authors.lastname: Sanada
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C497440:NFIL3 protein, human; D018696:Neuroprotective Agents; C497441:Nfil3 protein, mouse
keywords: Amyotrophic Lateral Sclerosis (Lou Gehrig Disease); Clock Genes; NFIL3; Neurodegeneration; Neurodegenerative Diseases; Neuroprotection