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Neurodegenerative Diseases. (neurodegenerative + diseases)
Selected AbstractsThe expression of tubulin polymerization promoting protein TPPP/p25, is developmentally regulated in cultured rat brain oligodendrocytes and affected by proteolytic stressGLIA, Issue 16 2008Olaf Goldbaum Abstract The tubulin polymerization-promoting protein (TPPP)/p25, was identified as a brain specific protein, is associated with microtubules (MTs) in vitro and can promote abnormal MT assembly. Furthermore it has aggregation promoting properties and is a constituent in pathological protein deposits of neurodegenerative diseases. In the brain, TPPP/p25, is present in myelinating oligodendrocytes. Here we show, using cultured rat brain oligodendrocytes, that TPPP/p25, expression is increasing during development in culture, and particularly in immature cells is associated with the centrosome. MT binding properties in oligodendrocytes are rather low, however, when MTs are disassembled by nocodazole, TPPP/p25, accumulates in the perinuclear region. Treatment of oligodendrocytes with the proteasomal inhibitor MG-132 (1 ,M; 18 h) caused an increase in the amount of TPPP/p25, by about 40%, a decrease in its solubility, and led to the appearance of TPPP/p25,-positive cytoplasmic inclusions, which stained with thioflavin S and resembled inclusion bodies. Hence, it might be speculated that acute or chronic malfunction of the proteasomal degradation system, leading to the accumulation of aggregation prone proteins and the pro-aggregatory protein TPPP/p25, or to the aggregation of TPPP/p25, on its own, is causally related to the protein aggregation process in a variety of neurodegenerative diseases. © 2008 Wiley-Liss, Inc. [source] Progress towards achieving new vaccine and vaccination goalsINTERNAL MEDICINE JOURNAL, Issue 7 2003G. Ada Abstract Viral and bacterial vaccines, especially for childhood use, are one of the most successful public health measures of the last two centuries and have a good safety record. However, there are still many diseases that are caused by infectious agents for which vaccines are not available. Our increasing ability to manipulate the immune system offers hope that, in the future, at least some of these infections may be prevented by vaccination. A surprising recent development is the use of vaccine technology to test whether a range of other generally non-communicable diseases can be prevented (or at least controlled) in this way. Investigation of these diseases is still mainly at the experimental level, however the list includes different types of cancers, allergies, drug addiction and neurodegenerative diseases. (Intern Med J 2003; 33: 297,304) [source] Hexokinase II gene transfer protects against neurodegeneration in the rotenone and MPTP mouse models of Parkinson's disease,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010Juan Carlos Corona Abstract A typical feature of Parkinson's disease is the progressive loss of dopaminergic neurons in the substantia nigra, in which inhibition of mitochondrial complex I activity may play an important role. Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibit the mitochondrial complex I and they cause the death of substantia nigra dopaminergic neurons, thereby providing acute murine models of Parkinson's disease. We have found that increasing mitochondrial hexokinase II activity can prevent cell death in neuronal cultures treated with rotenone. As a result, we have studied the effects of hexokinase II gene transfer in vivo using a herpes simplex virus type 1 (HSV-1) amplicon vector. The placHK2 amplicon vector was injected into substantia nigra of mice that were subsequently administered rotenone or MPTP. Overexpression of hexokinase II prevented both rotenone and MPTP-induced dopaminergic neuronal cell death, as well as reducing the associated motor defects. Our results provide the first proof-of-principle that hexokinase II protects against dopaminergic neurodegeneration in vivo, emphasizing the role of this enzyme in promoting neuronal survival. Thus, the increase of hexokinase II expression by gene transfer or other means represents a promising approach to treat Parkinson's and other neurodegenerative diseases. © 2010 Wiley-Liss, Inc. [source] Neural differentiation and potential use of stem cells from the human umbilical cord for central nervous system transplantation therapyJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2008Choon Bing Low Abstract The human umbilical cord is a rich source of autologous stem and progenitor cells. Interestingly, subpopulations of these, particularly mesenchymal-like cells from both cord blood and the cord stroma, exhibited a potential to be differentiated into neuron-like cells in culture. Umbilical cord blood stem cells have demonstrated efficacy in reducing lesion sizes and enhancing behavioral recovery in animal models of ischemic and traumatic central nervous system (CNS) injury. Recent findings also suggest that neurons derived from cord stroma mesenchymal cells could alleviate movement disorders in hemiparkinsonian animal models. We review here the neurogenic potential of umbilical cord stem cells and discuss possibilities of their exploitation as an alternative to human embryonic stem cells or neural stem cells for transplantation therapy of traumatic CNS injury and neurodegenerative diseases. © 2008 Wiley-Liss, Inc. [source] AUF-1 mediates inhibition by nitric oxide of lipopolysaccharide-induced matrix metalloproteinase-9 expression in cultured astrocytesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2006Wenlan Liu Abstract Neuroinflammatory diseases are associated with increased production of matrix metalloproteinase-9 (MMP-9) and excessive generation of nitric oxide (NO). NO hasbeen reported to have variable effects on MMP-9 gene expression and activation in various cell types. Inthe present study, we investigated the effect of NOon MMP-9 expression in primary cortical astrocytes. Zymography and real-time PCR showed that lipopolysaccharide (LPS) dramatically increased latent MMP-9 gelatinolytic activity and MMP-9 mRNA expression. By using the NO donor DETA NONOate, we observed a dose-dependent inhibition of MMP-9 induction by LPS. Active forms of MMP-9 were not found by zymography after NO treatment. The MEK1/2 inhibitor U0126 completely inhibited LPS-induced MMP-9, which was partially inhibited by the p38 MAPK inhibitor SB203580. NO had no effect on LPS-stimulated ERK1/2 and p38 MAPK activation, suggesting that the inhibitory action of NO occurs downstream of MAPK cascades. Real-time PCR analysis showed that NO accelerated the degradation of MMP-9 mRNA after LPS induction. Western blotting and pull-down assay demonstrated that NO increased AUF-1 expression as well as its specific binding to the MMP-9 gene 3,-untranslated region. Knockdown of AUF-1 with siRNA partially reversed the inhibitory action of NO on LPS-stimulated MMP-9 induction. We conclude that NO does not activate MMP-9 in astrocyte cultures but reduces LPS-induced MMP-9 expression via accelerating MMP-9 mRNA degradation, which is partially mediated by AUF-1. Our results suggest that elevated NO concentrations may suppress MMP-9 and restrict the inflammatory response in neurodegenerative diseases. © 2006 Wiley-Liss, Inc. [source] Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005Akihito Ishigami Abstract Citrullinated proteins are the products of a posttranslational process in which arginine residues undergo modification into citrulline residues when catalyzed by peptidylarginine deiminases (PADs) in a calcium ion-dependent manner. In our previous report, PAD2 expressed mainly in the rat cerebrum became activated early in the neurodegenerative process. To elucidate the involvement of protein citrullination in human neuronal degeneration, we examined whether citrullinated proteins are produced during Alzheimer's disease (AD). By Western blot analysis with antimodified citrulline antibody, citrullinated proteins of varied molecular weights were detected in hippocampal tissues from patients with AD but not normal humans. Two of the citrullinated proteins were identified as vimentin and glial fibrillary acidic protein (GFAP) by using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. Interestingly, PAD2 was detected in hippocampal extracts from AD and normal brains, but the amount of PAD2 in the AD tissue was markedly greater. Histochemical analysis revealed citrullinated proteins throughout the hippocampus, especially in the dentate gyrus and stratum radiatum of CA1 and CA2 areas. However, no citrullinated proteins were detected in the normal hippocampus. PAD2 immunoreactivity was also ubiquitous throughout both the AD and the normal hippocampal areas. PAD2 enrichment coincided well with citrullinated protein positivity. Double immunofluorescence staining revealed that citrullinated protein- and PAD2-positive cells also coincided with GFAP-positive cells, but not all GFAP-positive cells were positive for PAD2. As with GFAP, which is an astrocyte-specific marker protein, PAD2 is distributed mainly in astrocytes. These collective results, the abnormal accumulation of citrullinated proteins and abnormal activation of PAD2 in hippocampi of patients with AD, strongly suggest that PAD has an important role in the onset and progression of AD and that citrullinated proteins may become a useful marker for human neurodegenerative diseases. © 2005 Wiley-Liss, Inc. [source] Chronic nicotine administration increases NGF-like immunoreactivity in frontoparietal cerebral cortexJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2003R. Martínez-Rodríguez Abstract Nicotine/nicotine agonists, which have been proposed as therapeutic agents for the treatment of Alzheimer's disease and other neurodegenerative disorders, produce a wide variety of effects on the nervous system. Some mechanisms involved remain poorly understood. In this work, immunohistochemical techniques were used to determine the effect of nicotine on nerve growth factor (NGF) in the frontoparietal (motor, somatosensory) brain cortex of the albino rat. Nicotine was chronically administered intraperitoneally using osmotic pumps (0.35 mg nicotine base/kg body weight/day for 14 days). An increase in the number and the immunoreaction intensity of NGF-like positive pyramidal and nonpyramidal neurons of these cortical areas was observed after treatment. Immunopositive astroglial cells were always seen in sections of treated animals but not in controls. The neuropil of control animals was, in general, devoid of reaction, but in treated animals, immunopositive prolongations were located randomly, some in close association with capillaries. At the electron microscopic level, these prolongations were demonstrated as belonging to neurons (dendrites and axons) and astroglial cells. Nicotinic activation of selected neurons and glial cells seems to trigger NGF/neurotrophic mechanisms, suggesting their use may be of benefit in prevention and treatment of neurodegenerative diseases. © 2003 Wiley-Liss, Inc. [source] | ||||||||||