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Vitamins and Hormones 2017One of the most characterized neurotrophic factors is brain-derived neurotrophic factor (BDNF), which regulates neuronal survival and differentiation, and functions in... (Review)
Review
One of the most characterized neurotrophic factors is brain-derived neurotrophic factor (BDNF), which regulates neuronal survival and differentiation, and functions in activity-dependent plasticity processes such as long-term potentiation, long-term depression (LTD), and learning memory. Similar to other growth factors, BDNF protein is produced by transcriptional and translational mechanisms. Nevertheless, a posttranslational mechanism, the proteolytic conversion of precursor BDNF into at least two fragments, bioactive BDNF and the prodomain, has not been well elucidated. Recently, we demonstrated that the BDNF prodomain, which is named the BDNF propeptide, was endogenously secreted from neuronal cells and facilitated a cellular mechanism of LTD, suggesting the manner through which this posttranslational mechanism multiplies the biological actions of BDNF. In this chapter, we focus on the BDNF propeptide, especially in synaptic plasticity, and discuss the role of this molecule in the brain. The findings regarding the BDNF propeptide would provide new insights for understanding the mechanisms of action of the propeptides of growth factors as well as the biological roles of neurotrophins.
Topics: Amino Acid Substitution; Animals; Brain-Derived Neurotrophic Factor; Humans; Long-Term Synaptic Depression; Neuronal Plasticity; Neurons; Polymorphism, Genetic; Protein Interaction Domains and Motifs; Protein Precursors; Secretory Vesicles; Synaptic Transmission
PubMed: 28215295
DOI: 10.1016/bs.vh.2016.11.006 -
Frontiers in Bioengineering and... 2022Food is essential for human survival. Nowadays, traditional agriculture faces challenges in balancing the need of sustainable environmental development and the rising... (Review)
Review
Food is essential for human survival. Nowadays, traditional agriculture faces challenges in balancing the need of sustainable environmental development and the rising food demand caused by an increasing population. In addition, in the emerging of consumers' awareness of health related issues bring a growing trend towards novel nature-based food additives. Synthetic biology, using engineered microbial cell factories for production of various molecules, shows great advantages for generating food alternatives and additives, which not only relieve the pressure laid on tradition agriculture, but also create a new stage in healthy and sustainable food supplement. The biosynthesis of food components (protein, fats, carbohydrates or vitamins) in engineered microbial cells often involves cellular central metabolic pathways, where common precursors are processed into different proteins and products. Quantitation of the precursors provides information of the metabolic flux and intracellular metabolic state, giving guidance for precise pathway engineering. In this review, we summarized the quantitation methods for most cellular biosynthetic precursors, including energy molecules and co-factors involved in redox-reactions. It will also be useful for studies worked on pathway engineering of other microbial-derived metabolites. Finally, advantages and limitations of each method are discussed.
PubMed: 35360389
DOI: 10.3389/fbioe.2022.849177 -
Biochemical and Biophysical Research... Apr 2024Nicotinamide adenine dinucleotide (NAD) is the fundamental molecule that performs numerous biological reactions and is crucial for maintaining cellular homeostasis.... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) is the fundamental molecule that performs numerous biological reactions and is crucial for maintaining cellular homeostasis. Studies have found that NAD decreases with age in certain tissues, and age-related NAD depletion affects physiological functions and contributes to various aging-related diseases. Supplementation of NAD precursor significantly elevates NAD levels in murine tissues, effectively mitigates metabolic syndrome, enhances cardiovascular health, protects against neurodegeneration, and boosts muscular strength. Despite the versatile therapeutic functions of NAD in animal studies, the efficacy of NAD precursors in clinical studies have been limited compared with that in the pre-clinical study. Clinical studies have demonstrated that NAD precursor treatment efficiently increases NAD levels in various tissues, though their clinical proficiency is insufficient to ameliorate the diseases. However, the latest studies regarding NAD precursors and their metabolism highlight the significant role of gut microbiota. The studies found that orally administered NAD intermediates interact with the gut microbiome. These findings provide compelling evidence for future trials to further explore the involvement of gut microbiota in NAD metabolism. Also, the reduced form of NAD precursor shows their potential to raise NAD, though preclinical studies have yet to discover their efficacy. This review sheds light on NAD therapeutic efficiency in preclinical and clinical studies and the effect of the gut microbiota on NAD metabolism.
Topics: Mice; Animals; NAD; Dietary Supplements; Aging; Niacinamide; Nicotinamide Mononucleotide
PubMed: 38340651
DOI: 10.1016/j.bbrc.2024.149590 -
Human Pathology Mar 2023Clinical surveillance and follow-up of patients diagnosed with or at risk for urinary bladder cancers represent long-term, invasive, and costly processes for which... (Review)
Review
Clinical surveillance and follow-up of patients diagnosed with or at risk for urinary bladder cancers represent long-term, invasive, and costly processes for which supplemental biomarker information could help provide objective, personalized risk assessment. In particular, there are several precursors and possible precursors to urinary bladder cancer for which clinical behavior is heterogenous and interobserver variability in histopathologic diagnosis make it difficult to standardize management. This review seeks to highlight these precursor lesions from a diagnostic perspective (including flat urothelial lesions, papillary urothelial lesions, squamous lesions, and glandular lesions) and qualify known multiomic biomarkers that may help explain their behavior, predict patient risk, and acknowledge the nuance inherent to the question of whether these lesions are "benign" or "preneoplastic."
Topics: Humans; Urinary Bladder Neoplasms; Biomarkers; Urothelium
PubMed: 35716731
DOI: 10.1016/j.humpath.2022.06.006 -
ACS Omega Sep 2018In mass spectrometry (MS)-based proteomics, protein and peptide sequences are determined by the isolation and subsequent fragmentation of precursor ions. When an...
In mass spectrometry (MS)-based proteomics, protein and peptide sequences are determined by the isolation and subsequent fragmentation of precursor ions. When an isolation window captures only part of a precursor's isotopic distribution, the isotope distributions of the fragments depend on the subset of isolated precursor isotopes. Approximation of the expected isotope distributions of these fragments prior to sequence determination enables MS2 deisotoping, monoisotopic mass calculation, charge assignment of fragment peaks, and deconvolution of chimeric spectra. However, currently such methods do not exist, and precursor isotope distributions are often used as a proxy. Here, we present methods that approximate the isotope distribution of a biomolecule's fragment given its monoisotopic mass, the monoisotopic mass of its precursor, the set of isolated precursor isotopes, and optionally sulfur atom content. Our methods use either the Averagine model or splines, the latter of which have similar accuracy to the Averagine approach, but are 20 times faster to compute. Theoretical and approximated isotope distributions are consistent for fragments of in silico digested peptides. Furthermore, mass spectrometry experiments with the angiotensin I peptide and HeLa cell lysate demonstrate that the fragment methods match isotope peaks in MS2 spectra more accurately than the precursor Averagine approach. The algorithms for the approximation of fragment isotope distributions have been added to the OpenMS software library. By providing the means for analyzing fragment isotopic distributions, these methods will improve MS2 spectra interpretation.
PubMed: 30288463
DOI: 10.1021/acsomega.8b01649 -
Genes & Development Jan 2017The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease... (Review)
Review
The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear. Recent studies have identified distinct adipocyte precursor populations that are physiologically regulated and contribute to the development, maintenance, and expansion of adipocyte pools in mice. With new tools available, the properties of adipocyte precursors can now be defined, and the regulation and function of adipose plasticity in development and physiology can be explored.
Topics: Adipocytes, Brown; Adipocytes, White; Adipogenesis; Animals; Cell Differentiation; Humans; Research
PubMed: 28202540
DOI: 10.1101/gad.293704.116 -
Methods in Molecular Biology (Clifton,... 2023T lymphocytes (T cells) are essential components of the adaptive immune system; they serve multiple functions in responses to pathogens and to ensure immune homeostasis.... (Review)
Review
T lymphocytes (T cells) are essential components of the adaptive immune system; they serve multiple functions in responses to pathogens and to ensure immune homeostasis. Written for readers first entering this field of study, this chapter is a brief overview of the development of T cells in the thymus, from the entry of thymus-settling bone marrow-derived precursors to the egress of mature T cells. Surveyed topics include the differentiation and expansion of early precursors, the generation of the T cell antigen receptor repertoire, the selection of αβ T cell precursors, and their acquisition of functional competency.
Topics: Antigens; Cell Differentiation; Precursor Cells, T-Lymphoid; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, alpha-beta; Thymus Gland
PubMed: 36374448
DOI: 10.1007/978-1-0716-2740-2_1 -
International Journal of Molecular... Nov 2017Benzylisoquinoline alkaloids (BIAs) are among the most important plant secondary metabolites, in that they include a number of biologically active substances widely... (Review)
Review
Benzylisoquinoline alkaloids (BIAs) are among the most important plant secondary metabolites, in that they include a number of biologically active substances widely employed as pharmaceuticals. Isolation of BIAs from their natural sources is an expensive and time-consuming procedure as they accumulate in very low levels in plant. Moreover, total synthesis is challenging due to the presence of stereogenic centers. In view of these considerations, green and scalable methods for BIA synthesis using fully enzymatic approaches are getting more and more attention. The aim of this paper is to review fully enzymatic strategies for producing the benzylisoquinoline central precursor, ()-norcoclaurine and its derivatives. Specifically, we will detail the current status of synthesis of BIAs in microbial hosts as well as using isolated and recombinant enzymes.
Topics: Alkaloids; Bacteria; Benzylisoquinolines; Bioreactors; Escherichia coli; Plants; Recombinant Proteins; Saccharomyces cerevisiae; Tetrahydroisoquinolines
PubMed: 29156609
DOI: 10.3390/ijms18112464 -
Nature Reviews. Rheumatology Mar 2015Osteoclasts are cells of haematopoietic origin that are uniquely specialized to degrade bone. Under physiological conditions, the osteoclastogenesis pathway depends on... (Review)
Review
Osteoclasts are cells of haematopoietic origin that are uniquely specialized to degrade bone. Under physiological conditions, the osteoclastogenesis pathway depends on macrophage colony-stimulating factor 1 (CSF-1, also known as M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). However, an emerging hypothesis is that alternative pathways of osteoclast generation might be active during inflammatory arthritis. In this Perspectives article, we summarize the physiological pathway of osteoclastogenesis and then focus on experimental findings that support the hypothesis that infiltrating inflammatory cells and the cytokine milieu provide multiple routes to bone destruction. The precise identity of osteoclast precursor(s) is not yet known. We propose that myeloid cell differentiation during inflammation could be an important contributor to the differentiation of osteoclast populations and their associated pathologies. Understanding the dynamics of osteoclast differentiation in inflammatory arthritis is crucial for the development of therapeutic strategies for inflammatory joint disease in children and adults.
Topics: Animals; Arthritis; Bone Resorption; Humans; Inflammation; Osteoclasts
PubMed: 25422000
DOI: 10.1038/nrrheum.2014.198 -
The Journal of Nutrition Sep 2020A gluconeogenic precursor is a biochemical compound acted on by a gluconeogenic pathway enabling the net synthesis of glucose. Recognized gluconeogenic precursors in...
A gluconeogenic precursor is a biochemical compound acted on by a gluconeogenic pathway enabling the net synthesis of glucose. Recognized gluconeogenic precursors in fasting placental mammals include glycerol, lactate/pyruvate, certain amino acids, and odd-chain length fatty acids. Each of these precursors is capable of contributing net amounts of carbon to glucose synthesis via the tricarboxylic acid cycle (TCA cycle) because they are anaplerotic, that is, they are able to increase the pools of TCA cycle intermediates by the contribution of more carbon than is lost via carbon dioxide. The net synthesis of glucose from even-chain length fatty acids (ECFAs) in fasting placental mammals, via the TCA cycle alone, is not possible because equal amounts of carbon are lost via carbon dioxide as is contributed from fatty acid oxidation via acetyl-CoA. Therefore, ECFAs do not meet the criteria to be recognized as a gluconeogenic precursor via the TCA cycle alone. ECFAs are gluconeogenic precursors in organisms with a functioning glyoxylate cycle, which enables the net contribution of carbon to the intermediates of the TCA cycle from ECFAs and the net synthesis of glucose. The net conversion of ECFAs to glucose in fasting placental mammals via C3 metabolism of acetone may be a competent though inefficient metabolic path by which ECFA could be considered a gluconeogenic precursor. Defining a substrate as a gluconeogenic precursor requires careful articulation of the definition, organism, and physiologic conditions under consideration.
Topics: Acetyl Coenzyme A; Carbon; Citric Acid Cycle; Fatty Acids; Gluconeogenesis; Glucose; Glyoxylates; Humans; Oxidation-Reduction
PubMed: 32652033
DOI: 10.1093/jn/nxaa166