title: Mechanisms of aluminum-induced neurodegeneration in animals: Implications for Alzheimer's disease.
abstract: For four decades the controversial question concerning a possible role for aluminum neurotoxicity in contributing to the pathogenesis of Alzheimer's disease has been debated, and studies by different investigators have yielded contradictory results. The lack of sensitivity to aluminum neurotoxicity in transgenic mouse models of Alzheimer's disease has not allowed the system to be used to explore important aspects of this toxicity. Rabbits are particularly sensitive to aluminum neurotoxicity and they develop severe neurological changes that are dependent on dose, age and route of administration. The most prominent feature induced by aluminum in rabbit brain is a neurofibrillary degeneration that shares some similarity with the neurofibrillary tangles found in Alzheimer's disease patients. In the present review we discuss data from our laboratory and others, on the effects of aluminum on behaviour, neurologic function and morphology, using aluminum administered to rabbits via different routes. Finally, we will examine data on the possible cellular mechanisms underlying aluminum neurotoxicity, and potential neuroprotective strategies against aluminum toxicity.
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, VA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Savory
authors.forename: Mary M
authors.initials: MM
authors.lastname: Herman
authors.forename: Othman
authors.initials: O
authors.lastname: Ghribi
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors; D000072224:Bcl-2-Like Protein 11; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds / Q000633:toxicity*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D011753:Pyrones / Q000633:toxicity*; D011817:Rabbits; D051028:bcl-2-Associated X Protein / Q000187:drug effects
chemical_list: D016564:Amyloid beta-Protein Precursor; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009942:Organometallic Compounds; D011518:Proto-Oncogene Proteins; D011753:Pyrones; D051028:bcl-2-Associated X Protein; C067527:aluminum maltolate