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ISBN: 9782889195725 Year: 2015 Publisher: Frontiers Media SA
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When Ehrlich discovered the first evidence of the blood-brain barrier in 1885, he probably did not perceive the Great Wall that remained hidden from consciousness inside the central nervous system. Ehrlich had observed that acidic vital dyes did not stain the brain if they were injected into the blood stream. A century ago (1913), Goldman showed that the injection of trypan blue in the cerebrospinal fluid stained only the brain, but not the other organs. For almost a century it was thought that the blood-brain barrier (BBB) consisted in a physical barrier, resulting from the restricted permeability of the cerebral endothelial cell layer, as they are joined by tight junctions. However, as scientists are always looking for news in what is already discovered, in the end of the 20th century we had evidences that cerebral endothelial and glial cells express several drug metabolizing enzymes consisting in a second protection system: a metabolic barrier. Furthermore, the drugs and their metabolites must overcome the activity of several multidrug resistance proteins that function as ATP-dependent efflux pumps, consisting in the third line of defence: the active barrier. Therefore, the way the BBB actually works should be better explained. Several endogenous compounds, as well as xenobiotics, may be activated by enzymes of the metabolic barrier, generating reactive oxygen species that could damage neurons. Therefore, endothelial and glial cells possess endogenous protecting compounds and enzymes against oxidants, consisting in an antioxidant barrier. When all these systems fail, glial cells, mainly microglia, secrete cytokines in an attempt to crosstalk with defence cells asking for help, which consists in an immune barrier. In cerebral regions that are devoid of the physical barrier, such as circumventricular organs, the metabolic, active, antioxidant and immune barriers are reinforced. It is important to understand how cells involved in the BBB interact with one another and the dynamic mechanisms of their functions. This Research Topic published in this e-Book considers recent highlights in BBB structure, cell and molecular biology, biotransformation, physiology, pathology, pharmacology, immunology and how these basic knowledges can be applied in drug discovery and clinical researches, rewriting what is already written, and paving the way that goes to the Great Wall in the Frontiers of the Brain in this new century that is just beginning.
Neuroscience --- Human Anatomy & Physiology --- Health & Biological Sciences --- glial cells --- Stroke --- Cerebral endothelial cells --- BBB --- Oxidative Stress --- Glioma --- Blood Brain Barrier --- xenobiotic metabolizing enzymes --- Parkinsons disease --- Neuroinflammation
Book
ISBN: 3039216791 3039216783 Year: 2019 Publisher: MDPI - Multidisciplinary Digital Publishing Institute
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In the last two decades, due to the continuous increase of lifespans in Westernsocieties, and the consequent growing of the elderly population, have witnessedan increase in the number of studies on biological and molecular factors able topromote healthy aging and reach longevity. The study of the genetic componentof human longevity demonstrated that it accounts for 25% of intra populationphenotype variance. The efforts made to characterize the genetic determinantssuggested that the maintenance of cellular integrity, inflammation, oxidativestress response, DNA repair, as well as the use of nutrients, represent the mostimportant pathways correlated with a longer lifespan. However, although aplethora of variants were indicated to be associated with human longevity, onlyvery few were successfully replicated in different populations, probably becauseof population specificity, missing heritability as well as a complex interactionamong genetic factors with lifestyle and cultural factors, which modulate theindividual chance of living longer. Thus, many challenges remain to be addressedin the search for the genetic components of human longevity. This Special Issue isaimed to unify the progress in the analysis of the genetic determinants of humanlongevity, to take stock of the situation and point to future directions of the field.We invite submissions for reviews, research articles, short-communicationsdealing with genetic association studies in human longevity, including all types ofgenetic variation, as well as the characterization of longevity-related genes.
unknown zygosity --- exceptional longevity --- TERC --- xenobiotic-metabolizing enzymes --- lifespan --- gender-specific association --- long-livers --- polymorphism --- cumulative incidence curves --- cardiovascular health --- twins --- genetic determinants of human longevity --- TERT --- SNP --- moonlighting protein --- longevity --- genomics --- APOE --- polygenic risk score --- signal transduction --- xenobiotics --- survival --- IPMK --- genetic variation --- genetic association study --- molecular senescence --- zygosity --- longevity-related genes --- age-stratification --- lipid profile --- mortality --- apolipoprotein E --- aging --- model systems --- leukocyte telomere length --- inositol phosphates --- human lifespan --- populations
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