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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Alzheimer --- dementia --- microtubules --- neurodegeneration --- tau --- tauopathies

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The coordinated action of the different cytoskeletal polymers--microtubules, actin filaments and neurofilaments-- is essential for the establishment, remodeling and maintenance of neuronal architecture throughout the neuron lifetime. Neurons are among the most polarized cells, with a long thin axon and multiple thicker and shorter dendrites. Achieving this complex morphology, and the precise and accurate formation of an intricate network of synaptic contacts is critical for the proper transmission and reception of signals in the brain. Neuronal polarization precedes axon outgrowth and the subsequent differentiation of short neurites into dendrites, as part of the neuronal differentiation program that involves both intrinsic and extrinsic signals that converge at the cytoskeletal level. Growth cones, which are sensory and locomotor structures located at the tip of growing axons, are key elements in the transduction of extracellular cues into cytoskeletal changes, guiding axons to their right destinations. Neuronal migration, another crucial process during brain development, occurs in close coordination with neuronal differentiation. Migration involves as well an extensive rearrangement of neuronal cell shape that relies on cytoskeleton reorganization. Further processes, such as dendritic spine formation and growth, establishment of synaptic contacts or synaptic plasticity in mature neurons also depend on cytoskeletal dynamics. Fine-tune regulation of neuronal cytoskeleton is therefore crucial for the maintenance of neuronal integrity and functionality. Mutations in genes that code for cytoskeletal proteins often have deleterious effects in neurons, such as abnormal migration or differentiation, deficient axonal transport of organelles and synaptic vesicles, or impaired synaptic signaling. Several human Nervous System disorders, including neurodevelopmental, psychiatric, and neurodegenerative diseases, have been linked to cytoskeletal dysfunction. Cytoskeletal reorganization is also crucial to regulate nerve cell repair following Nervous System injury. Many of the pathways that control cell-intrinsic axon regeneration lead to axon cytoskeletal remodeling. Moreover, most extracellular cues that inhibit regeneration of damaged axons in Central Nervous System following traumatic injury or neurodegeneration, are known to modulate cytoskeletal dynamics and organization. Based on these findings, regulators of cytoskeleton dynamics have emerged as promising therapeutic targets in several brain disorders and in the context of regeneration of injured axons. Hence, remodeling of neuronal cytoskeleton underlies all the dramatic morphological changes that occur in developing and adult neurons. Understanding the specific molecular mechanisms that control cytoskeleton rearrangements in neurons is far from complete. This Frontiers Research Topic gathers a selection of articles focused on the diverse and key roles of cytoskeleton in neuronal biology.

neuronal cytoskeleton --- astrocyte cytoskeleton --- microtubules (MTs) --- actin cytoskeleton --- tau --- neuron

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The family of proteins called the tubulin and the microtubules they form when they aggregate are extremely important in the cell and, as we are increasingly learning, important in diseases that afflict so many. This field of investigation is a testament to how important both basic and clinical sciences are in understanding disease mechanisms and making inroads into therapies. Microtubule Targets in Cancer Therapy presents the first comprehensive exploration of the dynamic potential of microtubules anti-cancer targets. Written by leading anti-cancer researchers, this groundbreaking volume collects the most current microtubule research available. Among the topics examined in this volume are compounds that interact with tubulin, mechanisms and regulation by microtubule-associated proteins and drugs, MAPs, the tubulin superfamily its isotopes, peptides and depsipeptides, and neurodegenerative diseases. Without the basic scientific knowledge that has been accumulated – to which the contributors of this work have contributed greatly – we would not be in the position we find ourselves as we increasingly understand disease and advancing therapies. Microtubule Targets in Cancer Therapy contributes to this new knowledge, and the text will be an invaluable resource for cancer researchers, oncologists, pharmacologists, and medical chemists.

Microtubules. --- Cancer --- Treatment. --- Cancer therapy --- Cancer treatment --- Cytotubules --- Therapy --- Cancer Research. --- Medicinal Chemistry. --- Medicine. --- Cancer research. --- Pharmacology. --- Medicinal chemistry. --- Oncology. --- Biomedicine. --- Pharmacology/Toxicology. --- Cell organelles

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reviews. The SAR data are discussed in light of the structural information available for each agent. The second chapter focuses on the total synthesis of the marine sponge-derived polyketide discodermolide. A comprehensive survey of the synthetic chemistry efforts of several groups over a 14-year period is provided together with a comparison of the different approaches. The third chapter describes a comprehensive study of the mechanisms of activity of microtubules stabilizing drugs. Thermodynamic, kinetic, structural and functional data on microtubules stabilizing drugs are discussed in an interdisciplinary manner to generate a “time-resolved” picture of the interaction of the drugs with different tubulin forms. The fourth and fifth chapters review the efforts and achievements made in the characterization of the structure of the complexes of tubulin with microtubules stabilizing agents by NMR (Chapter 4) and EM (Chapter 5). Especially evident is the discrepancy of the results obtained for epothilones, where the two techniques deliver radically different structures of the bound drug. Both NMR and EM models are, however, able to explain a consistent set of SAR data. The authors of the two chapters discuss critically the advantages and limitations of each methodology.

Tubulins --- Stabilizing agents --- Microtubules --- Chemistry --- Tubulin --- Nerve Tissue Proteins --- Microtubule Proteins --- Natural Science Disciplines --- Cytoskeleton --- Proteins --- Cytoplasmic Structures --- Disciplines and Occupations --- Cytoskeletal Proteins --- Biopolymers --- Amino Acids, Peptides, and Proteins --- Cytoplasm --- Polymers --- Macromolecular Substances --- Chemicals and Drugs --- Intracellular Space --- Cellular Structures --- Cells --- Anatomy --- Animal Biochemistry --- Pharmacy, Therapeutics, & Pharmacology --- Chemical Engineering --- Chemical & Materials Engineering --- Health & Biological Sciences --- Human Anatomy & Physiology --- Engineering & Applied Sciences --- Microtubules. --- Stabilizing agents. --- Tubulins. --- Agents, Stabilizing --- Stabilizers (Chemistry) --- Cytotubules --- Microtubule proteins --- Chemistry. --- Cancer research. --- Analytical chemistry. --- Organic chemistry. --- Medicinal chemistry. --- Biochemistry. --- Medicinal Chemistry. --- Biochemistry, general. --- Cancer Research. --- Organic Chemistry. --- Analytical Chemistry. --- Chemicals --- Cell organelles --- Oncology. --- Chemistry, Organic. --- Analytical biochemistry. --- Analytic biochemistry --- Biochemistry --- Chemistry, Analytic --- Organic chemistry --- Tumors --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Biology --- Medical sciences --- Composition --- Bioanalytic chemistry --- Bioanalytical chemistry --- Analytical chemistry --- Analysis, Chemical --- Analytic chemistry --- Chemical analysis --- Cancer research --- Chemistry, Medical and pharmaceutical --- Chemistry, Pharmaceutical --- Drug chemistry --- Drugs --- Medical chemistry --- Medicinal chemistry --- Pharmacochemistry

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Lignans are a class of natural products found mainly in plants. They have a wide variety of structures and exhibit a range of potent biological activities. Lignans are also well-known components of a number of widely eaten foods and are frequently studied for their dietary impact. Owing to these factors, lignans have been extensively studied by scientists from a large number of disciplines. This collection of research and review articles describes topics ranging in scope from the recent isolation and structural elucidation of new lignans, strategies towards the chemical synthesis of lignans, assessment of their biological activities and potential for further therapeutic development. Research showing the impact of lignans in the food and agricultural industries is also presented.

taste-active compound --- heilaohu --- 9-norlignans --- antioxidant activity --- drug-like --- human health --- chemometrics --- lignan --- bitterness --- red-flowered Chinese magnolia vine --- antioxidant --- ruminant --- secoisolariciresinol diglucoside --- quantification --- intermolecular interactions --- cattle --- anti-inflammatory activity --- acyl-Claisen --- LOX --- seed --- food groups --- microtubules --- anti-proliferative --- acetylcholinesterase inhibitors --- flax --- arylnaphthalene lignan --- epiboly --- aryldihydronaphthalene lignan --- multiple bioactive components --- enterolignan --- total synthesis --- genetic --- synthesis --- cultivated --- cell cycle --- chronic diseases --- national databases --- oxidation --- chemical components --- molecular dynamics --- COX --- lignans --- hydroxycinnamic acid --- chemical structures --- Chinese magnolia vine --- stereoselective synthesis --- sPLA2 --- Bursera fagaroides --- in silico studies --- antibacterial activity --- semisynthesis --- dibenzyl butyrolactones --- flavonoid glycoside --- lignan glycoside --- chemical characterization --- hydroxymatairesinol --- podophyllotoxin --- Lespedeza cuneata --- Bursera --- oak ageing --- Schisandrae Chinensis Fructus --- F-actin --- cultivar --- UHPLC-MS/MS --- bioactivity --- podophyllotoxin-type lignans --- harmonized databases --- graph theory --- antioxidants --- health promotion --- simultaneous quantitation --- natural products --- dietary intake --- cell migration --- Lignan --- chemical space --- diet --- Lauraceae --- pharmacokinetic --- cytotoxicity --- tujia ethnomedicine --- flavonolignans --- flavonol --- adipocyte and osteoblast differentiation --- Burseraceae --- environment --- dietary lignans --- phytochemical analysis --- Schisandra chinensis --- animal health --- neolignans --- Schisandra rubriflora --- cancer --- norlignans --- wild