title: Aluminum, the genetic apparatus of the human CNS and Alzheimer's disease (AD).
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.
authors.affiliation: Alchem Biotech, Toronto, ON M5S 1A8, Canada.
authors.forename: A I
authors.initials: AI
authors.lastname: Pogue
authors.affiliation: Alchem Biotech, Toronto, ON M5S 1A8, Canada; Neuroscience Center and the Departments of Neurology and Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. Electronic address: wlukiw@lsuhsc.edu.
authors.forename: W J
authors.initials: WJ
authors.lastname: Lukiw
mesh_terms: D000375:Aging / Q000235:genetics; D017607:Aluminum Compounds / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000235:genetics*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D009153:Mutagens / Q000633:toxicity*
chemical_list: D017607:Aluminum Compounds; D035683:MicroRNAs; D009153:Mutagens
keywords: Aluminium; Aluminum; Alzheimer's disease; Analyse miARN; DNA array; Genotoxicity; Génotoxicité; Human biochemical individuality; Maladie d’Alzheimer; MicroARN; Molécules pro-inflammatoires; NF-kB; Pro-inflammatory; Self biochimique; miRNA array; microRNA (miRNA)