Adv Exp Med Biol
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TrkB is the cognate receptor for brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family involved in neuronal survival, neurogenesis and synaptic plasticity. BDNF has been shown to protect photoreceptors from light-induced retinal degeneration (LIRD) and to improve ganglion cell survival following optic nerve damage. However, the utility of BDNF as a retinal neuroprotectant is limited by its short half-life, inability to cross the blood-brain and blood-retinal barriers, and activation of the proapoptotic p75 neurotrophin receptor. ⋯ The compound can pass the blood-brain and blood-retinal barriers when administered systemically and reduces kainic acid-induced neuronal cell death in a TrkB-dependent manner. Systemic administration of HIOC mitigates LIRD, assessed electrophysiologically and morphometrically. Hence, NAS may function as an endogenous circadian neurotrophin-like compound and HIOC is a good lead compound for further drug development for treatment of retinal degenerative diseases.
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Once viewed as part of the "dark matter" of genome, long noncoding RNAs (lncRNAs), which are mRNA-like but lack open reading frames, have emerged as an integral part of the mammalian transcriptome. Recent work demonstrated that lncRNAs play multiple structural and functional roles, and their analysis has become a new frontier in biomedical research. In this chapter, we provide an overview of different lncRNA families, describe methodologies available to study lncRNA-protein and lncRNA-DNA interactions systematically, and use well-studied lncRNAs as examples to illustrate their functional importance during normal development and in disease states.
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Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. ⋯ While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides are likely to emerge as neural and endocrine messengers in orchestrating the microbiota-gut-brain axis in health and disease.
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In general protein posttranslation modifications (PTMs) involve the covalent addition of functional groups or molecules to specific amino acid residues in proteins. These modifications include phosphorylation, glycosylation, S-nitrosylation, acetylation, lipidation, among others (Angew Chem Int Ed Engl 44(45):7342-7372, 2005). Although other amino acids can undergo different kinds of oxidative posttranslational modifications (oxPTMs) (Exp Gerontol 36(9):1495-1502, 2001), in this chapter oxPTM will be considered specifically related to Cysteine oxidation, and redox proteomics here is translated as a comprehensive investigation of oxPTMs, in biological systems, using diverse technical approaches. ⋯ Therefore, the identification and localization of oxPTMs within cellular milieu became critical to understand redox regulation of proteins in physiological and pathological conditions, and consequently an important information to develop better strategies for treatment and prevention of diseases associated with oxidative stress. There is a wide range of techniques available to investigate oxPTMs, including gel-based and non-gel-based separation approaches to be combined with sophisticated methods of detection, identification, and quantification of these modifications. The strategies and approaches to study oxPTMs and the respective applications related to physiological and pathological conditions will be discussed in more detail in this chapter.