Open AccessJournal Article
Intramuscular desferrioxamine in patients with Alzheimer's disease
TLDR
In this paper, a single-blind study was conducted to investigate whether the progression of dementia could be slowed by the trivalent ion chelator, desferrioxamine.Abstract:
Although epidemiological and biochemical evidence suggests that aluminium may be associated with Alzheimer's disease (AD), there is no convincing proof of a causal link for aluminium in disease progression. We have completed a two year, single-blind study to investigate whether the progression of dementia could be slowed by the trivalent ion chelator, desferrioxamine. 48 patients with probable AD were randomly assigned to receive desferrioxamine (125 mg intramuscularly twice daily, 5 days per week, for 24 months), oral placebo (lecithin), or no treatment. No significant differences in baseline measures of intelligence, memory, or speech ability existed between groups. Activities of daily living were assessed and videorecorded at 6, 12, 18, and 24 month intervals. There were no differences in the rate of deterioration of patients receiving either placebo or no treatment. Desferrioxamine treatment led to significant reduction in the rate of decline of daily living skills as assessed by both group means (p = 0.03) and variances (p less than 0.04). The mean rate of decline was twice as rapid for the no-treatment group. Appetite (n = 4) and weight (n = 1) loss were the only reported side-effects. We conclude that sustained administration of desferrioxamine may slow the clinical progression of the dementia associated with AD.read more
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Neurodegenerative diseases and oxidative stress.
TL;DR: Oxidative stress has been implicated in the progression of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and different strategies, including novel metal–protein attenuating compounds aimed at a variety of targets have shown promise in clinical studies.
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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Brent R. Stockwell,José Pedro Friedmann Angeli,Hülya Bayır,Ashley I. Bush,Marcus Conrad,Scott J. Dixon,Simone Fulda,Susan Gascon,Stavroula K. Hatzios,Valerian E. Kagan,Kay Noel,Xuejun Jiang,Andreas Linkermann,Maureen E. Murphy,Michael Overholtzer,Atsushi Oyagi,Gabriela Carolina Pagnussat,Jason Park,Qitao Ran,Craig S. Rosenfeld,Konstantin Salnikow,Daolin Tang,Daolin Tang,Frank M. Torti,Suzy V. Torti,Shinya Toyokuni,K. A. Woerpel,Donna D. Zhang +27 more
TL;DR: The mechanisms underlying ferroptosis are reviewed, connections to other areas of biology and medicine are highlighted, and tools and guidelines for studying this emerging form of regulated cell death are recommended.
Journal ArticleDOI
Oxidative stress hypothesis in alzheimer's disease
TL;DR: Supporting indirect evidence comes from a variety of in vitro studies showing that free radicals are capable of mediating neuron degeneration and death, suggesting that therapeutic efforts aimed at removal of ROS or prevention of their formation may be beneficial in AD.
Journal ArticleDOI
Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells.
TL;DR: It is shown that dithiocarbamates and metal chelators can potently block the activation of nuclear factor kappa B (NF-kappa B), a transcription factor involved in human immunodeficiency virus type 1 (HIV-1) expression, signaling, and immediate early gene activation during inflammatory processes.
Journal ArticleDOI
Treatment with a Copper-Zinc Chelator Markedly and Rapidly Inhibits β-Amyloid Accumulation in Alzheimer's Disease Transgenic Mice
Robert A. Cherny,Craig S. Atwood,Michel Xilinas,Danielle N. Gray,Walton D. Jones,Catriona McLean,Kevin J. Barnham,Irene Volitakis,Fiona W. Fraser,Young-Seon Kim,Xudong Huang,Lee E. Goldstein,Robert D. Moir,James Lim,Konrad Beyreuther,Hui Zheng,Rudolph E. Tanzi,Colin L. Masters,Ashley I. Bush,Ashley I. Bush +19 more
TL;DR: A 49% decrease in brain Abeta deposition is reported in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator, support targeting the interactions of Cu and Zn with Abeta as a novel therapy for the prevention and treatment of AD.
References
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Journal ArticleDOI
Clinical diagnosis of Alzheimer's disease : report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
Guy M. McKhann,David A. Drachman,Marshall F. Folstein,Robert Katzman,Donald L. Price,Emanuel M. Stadlan +5 more
TL;DR: The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information becomes available.
Journal ArticleDOI
Neurodegenerative diseases and oxidative stress.
TL;DR: Oxidative stress has been implicated in the progression of Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and different strategies, including novel metal–protein attenuating compounds aimed at a variety of targets have shown promise in clinical studies.
Journal ArticleDOI
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Brent R. Stockwell,José Pedro Friedmann Angeli,Hülya Bayır,Ashley I. Bush,Marcus Conrad,Scott J. Dixon,Simone Fulda,Susan Gascon,Stavroula K. Hatzios,Valerian E. Kagan,Kay Noel,Xuejun Jiang,Andreas Linkermann,Maureen E. Murphy,Michael Overholtzer,Atsushi Oyagi,Gabriela Carolina Pagnussat,Jason Park,Qitao Ran,Craig S. Rosenfeld,Konstantin Salnikow,Daolin Tang,Daolin Tang,Frank M. Torti,Suzy V. Torti,Shinya Toyokuni,K. A. Woerpel,Donna D. Zhang +27 more
TL;DR: The mechanisms underlying ferroptosis are reviewed, connections to other areas of biology and medicine are highlighted, and tools and guidelines for studying this emerging form of regulated cell death are recommended.
Journal ArticleDOI
Cerebral blood flow in dementia.
Vladimir Hachinski,L. D. Iliff,E. Zilhka,G. H. Du Boulay,V. L. McAllister,John Marshall,R. R. Russell,L. Symon +7 more
TL;DR: Cerebral blood flow per 100 gm brain per minute was normal in the primary degenerative group but low in the multi-infarct group, suggesting the blood flow is adequate for metabolic needs of the brain in patients withPrimary degenerative dementia but inadequate for those with multi- infarct dementia.