[
FEBS Lett,
2015]
The nervous system plays critical roles in the stress response. Animals can survive and function under harsh conditions, and resist and recover from injuries because neurons perceive and respond to various stressors through specific regulatory mechanisms. Caenorhabditis elegans has served as an excellent model to discover fundamental mechanisms underlying the neuronal response to stress. The basic physiological processes that C. elegans exhibits under stress conditions are similar to those observed in higher organisms. Many molecular pathways activated by environmental and cellular stresses are also conserved. In this review, we summarize major findings in examining neuronal responses to hypoxia, oxidative stress, osmotic stress, and traumatic injury. These studies from C. elegans have provided novel insights into our understanding of neuronal responses to stress at the molecular, cellular, and circuit levels.
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Biomolecules,
2020]
Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) is an essential cofactor that mediates numerous biological processes in all living cells. Multiple NAD<sup>+</sup> biosynthetic enzymes and NAD<sup>+</sup>-consuming enzymes are involved in neuroprotection and axon regeneration. The nematode <i>Caenorhabditis elegans</i> has served as a model to study the neuronal role of NAD<sup>+</sup> because many molecular components regulating NAD<sup>+</sup> are highly conserved. This review focuses on recent findings using <i>C. elegans</i> models of neuronal damage pertaining to the neuronal functions of NAD<sup>+</sup> and its precursors, including a neuroprotective role against excitotoxicity and axon degeneration as well as an inhibitory role in axon regeneration. The regulation of NAD<sup>+</sup> levels could be a promising therapeutic strategy to counter many neurodegenerative diseases, as well as neurotoxin-induced and traumatic neuronal damage.
[
Crit Rev Biochem Mol Biol,
2012]
The CCAAT box promoter element and NF-Y, the transcription factor (TF) that binds to it, were among the first cis-elements and trans-acting factors identified; their interplay is required for transcriptional activation of a sizeable number of eukaryotic genes. NF-Y consists of three evolutionarily conserved subunits: a dimer of NF-YB and NF-YC which closely resembles a histone, and the "innovative" NF-YA. In this review, we will provide an update on the functional and biological features that make NF-Y a fundamental link between chromatin and transcription. The last 25 years have witnessed a spectacular increase in our knowledge of how genes are regulated: from the identification of cis-acting sequences in promoters and enhancers, and the biochemical characterization of the corresponding TFs, to the merging of chromatin studies with the investigation of enzymatic machines that regulate epigenetic states. Originally identified and studied in yeast and mammals, NF-Y - also termed CBF and CP1 - is composed of three subunits, NF-YA, NF-YB and NF-YC. The complex recognizes the CCAAT pentanucleotide and specific flanking nucleotides with high specificity (Dorn et al., 1997; Hatamochi et al., 1988; Hooft van Huijsduijnen et al, 1987; Kim & Sheffery, 1990). A compelling set of bioinformatics studies clarified that the NF-Y preferred binding site is one of the most frequent promoter elements (Suzuki et al., 2001, 2004; Elkon et al., 2003; Marino-Ramirez et al., 2004; FitzGerald et al., 2004; Linhart et al., 2005; Zhu et al., 2005; Lee et al., 2007; Abnizova et al., 2007; Grskovic et al., 2007; Halperin et al., 2009; Hakkinen et al., 2011). The same consensus, as determined by mutagenesis and SELEX studies (Bi et al., 1997), was also retrieved in ChIP-on-chip analysis (Testa et al., 2005; Ceribelli et al., 2006; Ceribelli et al., 2008; Reed et al., 2008). Additional structural features of the CCAAT box - position, orientation, presence of multiple Transcriptional Start Sites - were previously reviewed (Dolfini et al., 2009) and will not be considered in detail here.