Progress in molecular biology and translational science
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Prog Mol Biol Transl Sci · Jan 2012
ReviewMembrane pores in the pathogenesis of neurodegenerative disease.
The neurodegenerative diseases described in this volume, as well as many nonneurodegenerative diseases, are characterized by deposits known as amyloid. Amyloid has long been associated with these various diseases as a pathological marker and has been implicated directly in the molecular pathogenesis of disease. However, increasing evidence suggests that these proteinaceous Congo red staining deposits may not be toxic or destructive of tissue. ⋯ These include irreversible insertion of the pores in lipid membranes, formation of heterodisperse pore sizes, inhibition by Congo red of pore formation, blockade of pores by zinc, and a relative lack of ion selectivity and voltage dependence. Although there exists some information about the physical structure of these pores, molecular modeling suggests that 4-6-mer amyloid subunits may assemble into 24-mer pore-forming aggregates. The molecular structure of these pores may resemble the β-barrel structure of the toxics pore formed by bacterial toxins, such as staphylococcal α-hemolysin, anthrax toxin, and Clostridium perfringolysin.
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Prog Mol Biol Transl Sci · Jan 2011
ReviewTherapeutic targets for neuroprotection and/or enhancement of functional recovery following traumatic brain injury.
Traumatic brain injury (TBI) is a significant public health concern. The number of injuries that occur each year, the cost of care, and the disabilities that can lower the victim's quality of life are all driving factors for the development of therapy. ⋯ This cascade of molecular, cellular, and systemwide changes involves plasticity in many different neurochemical systems, which represent putative targets for remediation or attenuation of neuronal injury. The purpose of this chapter is to highlight some of the promising molecular and cellular targets that have been identified and to provide an up-to-date summary of the development of therapeutic compounds for those targets.
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Heparin is frequently used in the treatment of cancer-associated thromboembolism. Accumulating clinical evidence indicates that cancer patients treated with unfractionated and low-molecular weight heparin (LMWH) survive longer than patients treated by other anticoagulants, especially patients in the early stage of the disease. ⋯ The non-anticoagulant activity of heparin on metastasis includes the ability to inhibit cell-cell-interaction through blocking of P- and L-selectin, to inhibit extracellular matrix protease heparanase, and to inhibit angiogenesis. This chapter summarizes current experimental evidence on the biology of heparin during cancer progression, with the focus on potential mechanism of heparin antimetastatic activity.
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Nephrogenic diabetes insipidus (NDI), which can be inherited or acquired, is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). Polyuria, with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. Nephrogenic failure to concentrate urine maximally may be due to a defect in vasopressin-induced water permeability of the distal tubules and collecting ducts, to insufficient buildup of the corticopapillary interstitial osmotic gradient, or to a combination of these two factors. ⋯ Neurohypophyseal diabetes insipidus is also a component of autosomal recessive Wolfram syndrome 1 or DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) (OMIM 222300)(1), an autosomal recessive disorder. Other inherited disorders with complex polyuro-polydipsic syndrome with loss of water, sodium, chloride, calcium, magnesium, and potassium include Bartter syndrome (OMIM 601678)(1) and cystinosis (OMIM 219800)(1), while long-term lithium administration is the main cause of acquired NDI. Here, we use the gene symbols approved by the HUGO Gene Nomenclature Committee (http://www.gene.ucl.ac.uk/nomenclature) and provide OMIM entry numbers [OMIM (Online Mendelian Inheritance in Man)(1); McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD), 2000; World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/].