Aluminum, the genetic apparatus of the human CNS and Alzheimer's disease (AD)
The genomes of eukaryotes orchestrate their expression to ensure an effective, homeostatic and functional gene signaling program, and this includes fundamentally altered patterns of transcription during aging, development, differentiation and disease. These actions constitute an extremely complex an...
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description | The genomes of eukaryotes orchestrate their expression to ensure an effective, homeostatic and functional gene signaling program, and this includes fundamentally altered patterns of transcription during aging, development, differentiation and disease. These actions constitute an extremely complex and intricate process as genetic operations such as transcription involve the very rapid translocation and polymerization of ribonucleotides using RNA polymerases, accessory transcription protein complexes and other interrelated chromatin proteins and genetic factors. As both free ribonucleotides and polymerized single-stranded RNA chains, ribonucleotides are highly charged with phosphate, and this genetic system is extremely vulnerable to disruption by a large number of electrostatic forces, and primarily by cationic metals such as aluminum. Aluminum has been shown by independent researchers to be particularly genotoxic to the genetic apparatus, and it has become reasonably clear that aluminum disturbs genetic signaling programs in the CNS that bear a surprising resemblance to those observed in Alzheimer's disease (AD) brain. This paper will focus on a discussion of two molecular-genetic aspects of aluminum genotoxicity: (1) the observation that micro-RNA (miRNA)-mediated global gene expression patterns in aluminum-treated transgenic animal models of AD (Tg-AD) strongly resemble those found in AD; and (2) the concept of “human biochemical individuality” and the hypothesis that individuals with certain gene expression patterns may be especially sensitive and perhaps predisposed to aluminum genotoxicity.
Le génome des eucaryotes orchestre son expression pour assurer un programme de signalisation génique efficace, homéostatique et fonctionnelle. Cela inclut les modèles avec des modifications fondamentales de la transcription au cours du vieillissement, le développement, la différenciation et les maladies. Ces mesures constituent un processus extrêmement complexe et intriqué car les mécanismes génétiques tels que la transcription impliquent la translocation et la polymérisation très rapide de ribonucléotides utilisant des ARN polymérases, des complexes protéiques de transcription accessoires et d’autres protéines de la chromatine ainsi que des facteurs génétiques. Les ribonucléotides libres ainsi que les chaînes simple brin d’ARN polymérisé sont très riches en phosphate et ce système génétique est extrêmement sensible aux perturbations créées par un grand nombre de f |
doi_str_mv | 10.1016/j.morpho.2016.01.001 |
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Le génome des eucaryotes orchestre son expression pour assurer un programme de signalisation génique efficace, homéostatique et fonctionnelle. Cela inclut les modèles avec des modifications fondamentales de la transcription au cours du vieillissement, le développement, la différenciation et les maladies. Ces mesures constituent un processus extrêmement complexe et intriqué car les mécanismes génétiques tels que la transcription impliquent la translocation et la polymérisation très rapide de ribonucléotides utilisant des ARN polymérases, des complexes protéiques de transcription accessoires et d’autres protéines de la chromatine ainsi que des facteurs génétiques. Les ribonucléotides libres ainsi que les chaînes simple brin d’ARN polymérisé sont très riches en phosphate et ce système génétique est extrêmement sensible aux perturbations créées par un grand nombre de forces électrostatiques, principalement par les métaux cationiques tels que l’aluminium. Il a été montré par différents groupes de chercheurs, que l’aluminium est particulièrement génotoxique pour l’appareil génétique. Il est devenu assez évident que l’aluminium perturbe les programmes de signalisation génétique dans le SNC qui ressemblent de façon surprenante à ceux observés dans la maladie d’Alzheimer (AD) cérébrale. Cet article se concentre sur une discussion de deux aspects de génétique moléculaire concernant la génotoxicité de l’aluminium : (1) l’observation que les profils d’expression globale des gènes médiée par les micro-ARN (miARN) par dans des modèles animaux transgéniques de maladie d’Alzheimer traités par l’aluminium (Tg-AD) ressemblent fortement à ceux trouvés dans cette maladie ; et (2) le concept de « l’individualité biochimique humaine » et l’hypothèse selon laquelle les individus avec certains profils d’expression génique peuvent être particulièrement sensibles et peut-être prédisposés à la génotoxicité de l’aluminium.</description><identifier>ISSN: 1286-0115</identifier><identifier>DOI: 10.1016/j.morpho.2016.01.001</identifier><identifier>PMID: 26969391</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Aging - genetics ; Aluminium ; Aluminum ; Aluminum Compounds - toxicity ; Alzheimer Disease - chemically induced ; Alzheimer Disease - genetics ; Alzheimer's disease ; Analyse miARN ; Animals ; Central Nervous System - drug effects ; Disease Models, Animal ; DNA array ; DNA Damage - drug effects ; Gene Expression Profiling ; Genetic Predisposition to Disease ; Genotoxicity ; Génotoxicité ; High-Throughput Nucleotide Sequencing ; Human biochemical individuality ; Humans ; Maladie d’Alzheimer ; Mice ; Mice, Transgenic ; MicroARN ; microRNA (miRNA) ; MicroRNAs - metabolism ; miRNA array ; Molécules pro-inflammatoires ; Mutagens - toxicity ; NF-kB ; Pro-inflammatory ; Self biochimique</subject><ispartof>Morphologie, 2016-06, Vol.100 (329), p.56-64</ispartof><rights>2016 Elsevier Masson SAS</rights><rights>Copyright © 2016 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c277t-e91b1f255e81867030c9e01204546058eb3922333ac0562d55b5d77c5e2c99293</citedby><cites>FETCH-LOGICAL-c277t-e91b1f255e81867030c9e01204546058eb3922333ac0562d55b5d77c5e2c99293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.morpho.2016.01.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26969391$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pogue, A.I.</creatorcontrib><creatorcontrib>Lukiw, W.J.</creatorcontrib><title>Aluminum, the genetic apparatus of the human CNS and Alzheimer's disease (AD)</title><title>Morphologie</title><addtitle>Morphologie</addtitle><description>The genomes of eukaryotes orchestrate their expression to ensure an effective, homeostatic and functional gene signaling program, and this includes fundamentally altered patterns of transcription during aging, development, differentiation and disease. These actions constitute an extremely complex and intricate process as genetic operations such as transcription involve the very rapid translocation and polymerization of ribonucleotides using RNA polymerases, accessory transcription protein complexes and other interrelated chromatin proteins and genetic factors. As both free ribonucleotides and polymerized single-stranded RNA chains, ribonucleotides are highly charged with phosphate, and this genetic system is extremely vulnerable to disruption by a large number of electrostatic forces, and primarily by cationic metals such as aluminum. Aluminum has been shown by independent researchers to be particularly genotoxic to the genetic apparatus, and it has become reasonably clear that aluminum disturbs genetic signaling programs in the CNS that bear a surprising resemblance to those observed in Alzheimer's disease (AD) brain. This paper will focus on a discussion of two molecular-genetic aspects of aluminum genotoxicity: (1) the observation that micro-RNA (miRNA)-mediated global gene expression patterns in aluminum-treated transgenic animal models of AD (Tg-AD) strongly resemble those found in AD; and (2) the concept of “human biochemical individuality” and the hypothesis that individuals with certain gene expression patterns may be especially sensitive and perhaps predisposed to aluminum genotoxicity.
Le génome des eucaryotes orchestre son expression pour assurer un programme de signalisation génique efficace, homéostatique et fonctionnelle. Cela inclut les modèles avec des modifications fondamentales de la transcription au cours du vieillissement, le développement, la différenciation et les maladies. Ces mesures constituent un processus extrêmement complexe et intriqué car les mécanismes génétiques tels que la transcription impliquent la translocation et la polymérisation très rapide de ribonucléotides utilisant des ARN polymérases, des complexes protéiques de transcription accessoires et d’autres protéines de la chromatine ainsi que des facteurs génétiques. Les ribonucléotides libres ainsi que les chaînes simple brin d’ARN polymérisé sont très riches en phosphate et ce système génétique est extrêmement sensible aux perturbations créées par un grand nombre de forces électrostatiques, principalement par les métaux cationiques tels que l’aluminium. Il a été montré par différents groupes de chercheurs, que l’aluminium est particulièrement génotoxique pour l’appareil génétique. Il est devenu assez évident que l’aluminium perturbe les programmes de signalisation génétique dans le SNC qui ressemblent de façon surprenante à ceux observés dans la maladie d’Alzheimer (AD) cérébrale. Cet article se concentre sur une discussion de deux aspects de génétique moléculaire concernant la génotoxicité de l’aluminium : (1) l’observation que les profils d’expression globale des gènes médiée par les micro-ARN (miARN) par dans des modèles animaux transgéniques de maladie d’Alzheimer traités par l’aluminium (Tg-AD) ressemblent fortement à ceux trouvés dans cette maladie ; et (2) le concept de « l’individualité biochimique humaine » et l’hypothèse selon laquelle les individus avec certains profils d’expression génique peuvent être particulièrement sensibles et peut-être prédisposés à la génotoxicité de l’aluminium.</description><subject>Aging - genetics</subject><subject>Aluminium</subject><subject>Aluminum</subject><subject>Aluminum Compounds - toxicity</subject><subject>Alzheimer Disease - chemically induced</subject><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer's disease</subject><subject>Analyse miARN</subject><subject>Animals</subject><subject>Central Nervous System - drug effects</subject><subject>Disease Models, Animal</subject><subject>DNA array</subject><subject>DNA Damage - drug effects</subject><subject>Gene Expression Profiling</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotoxicity</subject><subject>Génotoxicité</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Human biochemical individuality</subject><subject>Humans</subject><subject>Maladie d’Alzheimer</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>MicroARN</subject><subject>microRNA (miRNA)</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA array</subject><subject>Molécules pro-inflammatoires</subject><subject>Mutagens - toxicity</subject><subject>NF-kB</subject><subject>Pro-inflammatory</subject><subject>Self biochimique</subject><issn>1286-0115</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1PGzEQhn1oRdLAP0CVb4DUbGfs9e76ghSlLSCl5QCcLcc7IY72q_YuEv313TQpR06j0TzvjOZh7BwhQcDs6y6p29Bt20SMXQKYAOAHNkVRZHNAVBP2KcYdQIoyzU_YRGQ601LjlP1cVEPtm6H-wvst8WdqqPeO266zwfZD5O3m32A71Lbhy18P3DYlX1R_tuRrCheRlz6SjcQvF9-uTtnHja0inR3rjD39-P64vJ2v7m_ulovV3Ik87-ekcY0boRQVWGQ5SHCaAAWkKs1AFbSWWggppXWgMlEqtVZlnjtFwmkttJyxy8PeLrS_B4q9qX10VFW2oXaIBnMtlCwgUyOaHlAX2hgDbUwXfG3Dq0Ewe3lmZw7yzF6eATSjvDH2-XhhWNdUvoX-mxuB6wNA458vnoKJzlPjqPSBXG_K1r9_4S94noEX</recordid><startdate>201606</startdate><enddate>201606</enddate><creator>Pogue, A.I.</creator><creator>Lukiw, W.J.</creator><general>Elsevier Masson SAS</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201606</creationdate><title>Aluminum, the genetic apparatus of the human CNS and Alzheimer's disease (AD)</title><author>Pogue, A.I. ; Lukiw, W.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c277t-e91b1f255e81867030c9e01204546058eb3922333ac0562d55b5d77c5e2c99293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Aging - genetics</topic><topic>Aluminium</topic><topic>Aluminum</topic><topic>Aluminum Compounds - toxicity</topic><topic>Alzheimer Disease - chemically induced</topic><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer's disease</topic><topic>Analyse miARN</topic><topic>Animals</topic><topic>Central Nervous System - drug effects</topic><topic>Disease Models, Animal</topic><topic>DNA array</topic><topic>DNA Damage - drug effects</topic><topic>Gene Expression Profiling</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotoxicity</topic><topic>Génotoxicité</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Human biochemical individuality</topic><topic>Humans</topic><topic>Maladie d’Alzheimer</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>MicroARN</topic><topic>microRNA (miRNA)</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA array</topic><topic>Molécules pro-inflammatoires</topic><topic>Mutagens - toxicity</topic><topic>NF-kB</topic><topic>Pro-inflammatory</topic><topic>Self biochimique</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pogue, A.I.</creatorcontrib><creatorcontrib>Lukiw, W.J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Morphologie</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pogue, A.I.</au><au>Lukiw, W.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aluminum, the genetic apparatus of the human CNS and Alzheimer's disease (AD)</atitle><jtitle>Morphologie</jtitle><addtitle>Morphologie</addtitle><date>2016-06</date><risdate>2016</risdate><volume>100</volume><issue>329</issue><spage>56</spage><epage>64</epage><pages>56-64</pages><issn>1286-0115</issn><abstract>The genomes of eukaryotes orchestrate their expression to ensure an effective, homeostatic and functional gene signaling program, and this includes fundamentally altered patterns of transcription during aging, development, differentiation and disease. These actions constitute an extremely complex and intricate process as genetic operations such as transcription involve the very rapid translocation and polymerization of ribonucleotides using RNA polymerases, accessory transcription protein complexes and other interrelated chromatin proteins and genetic factors. As both free ribonucleotides and polymerized single-stranded RNA chains, ribonucleotides are highly charged with phosphate, and this genetic system is extremely vulnerable to disruption by a large number of electrostatic forces, and primarily by cationic metals such as aluminum. Aluminum has been shown by independent researchers to be particularly genotoxic to the genetic apparatus, and it has become reasonably clear that aluminum disturbs genetic signaling programs in the CNS that bear a surprising resemblance to those observed in Alzheimer's disease (AD) brain. This paper will focus on a discussion of two molecular-genetic aspects of aluminum genotoxicity: (1) the observation that micro-RNA (miRNA)-mediated global gene expression patterns in aluminum-treated transgenic animal models of AD (Tg-AD) strongly resemble those found in AD; and (2) the concept of “human biochemical individuality” and the hypothesis that individuals with certain gene expression patterns may be especially sensitive and perhaps predisposed to aluminum genotoxicity.
Le génome des eucaryotes orchestre son expression pour assurer un programme de signalisation génique efficace, homéostatique et fonctionnelle. Cela inclut les modèles avec des modifications fondamentales de la transcription au cours du vieillissement, le développement, la différenciation et les maladies. Ces mesures constituent un processus extrêmement complexe et intriqué car les mécanismes génétiques tels que la transcription impliquent la translocation et la polymérisation très rapide de ribonucléotides utilisant des ARN polymérases, des complexes protéiques de transcription accessoires et d’autres protéines de la chromatine ainsi que des facteurs génétiques. Les ribonucléotides libres ainsi que les chaînes simple brin d’ARN polymérisé sont très riches en phosphate et ce système génétique est extrêmement sensible aux perturbations créées par un grand nombre de forces électrostatiques, principalement par les métaux cationiques tels que l’aluminium. Il a été montré par différents groupes de chercheurs, que l’aluminium est particulièrement génotoxique pour l’appareil génétique. Il est devenu assez évident que l’aluminium perturbe les programmes de signalisation génétique dans le SNC qui ressemblent de façon surprenante à ceux observés dans la maladie d’Alzheimer (AD) cérébrale. Cet article se concentre sur une discussion de deux aspects de génétique moléculaire concernant la génotoxicité de l’aluminium : (1) l’observation que les profils d’expression globale des gènes médiée par les micro-ARN (miARN) par dans des modèles animaux transgéniques de maladie d’Alzheimer traités par l’aluminium (Tg-AD) ressemblent fortement à ceux trouvés dans cette maladie ; et (2) le concept de « l’individualité biochimique humaine » et l’hypothèse selon laquelle les individus avec certains profils d’expression génique peuvent être particulièrement sensibles et peut-être prédisposés à la génotoxicité de l’aluminium.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>26969391</pmid><doi>10.1016/j.morpho.2016.01.001</doi><tpages>9</tpages></addata></record> |
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subjects | Aging - genetics Aluminium Aluminum Aluminum Compounds - toxicity Alzheimer Disease - chemically induced Alzheimer Disease - genetics Alzheimer's disease Analyse miARN Animals Central Nervous System - drug effects Disease Models, Animal DNA array DNA Damage - drug effects Gene Expression Profiling Genetic Predisposition to Disease Genotoxicity Génotoxicité High-Throughput Nucleotide Sequencing Human biochemical individuality Humans Maladie d’Alzheimer Mice Mice, Transgenic MicroARN microRNA (miRNA) MicroRNAs - metabolism miRNA array Molécules pro-inflammatoires Mutagens - toxicity NF-kB Pro-inflammatory Self biochimique |
title | Aluminum, the genetic apparatus of the human CNS and Alzheimer's disease (AD) |
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