Your search for: 'author:("Butterfield, D. Allan")' has returned 19 results. (0.014s) Save search

Authors: Butterfield, D. Allan

Article Type: Obituary

DOI: 10.3233/JAD-2010-100246

Citation: Journal of Alzheimer's Disease, vol. 20, no. 1, pp. 3-4, 2010

Authors: Butterfield, D. Allan

Article Type: Review Article

Abstract: Oxidative stress, an overproduction of free radicals or a diminution of free radical scavenging ability relative to those of cognitively aged-matched controls, is widely recognized as a critical component of the pathogenesis and progression of Alzheimer’s disease (AD). This recognition arose in significant part from the work in the author’s laboratory, complemented by research from others’ laboratories. The Butterfield laboratory discovered the oxidative stress associated with oligomeric amyloid-β peptide manifested primarily as elevated oxidative modification of proteins and peroxidation of lipids. Such oxidative damage caused neuronal death, which undoubtedly underlies the progressive loss of cognition in AD. Identification of specific …oxidatively modified brain proteins in subjects with AD or amnestic mild cognitive impairment was achieved by the methods of redox proteomics, pioneered in the author’s laboratory. The importance and significance of the research emanating from the Butterfield laboratory rest on the paradigm shift of thinking regarding the roles of oxidative stress and resulting damage to key proteins and biochemical pathways in the pathogenesis and progression of AD. Predictions of future research directions also are presented. Given the enormous financial and personal burden placed upon citizens (and governments) of the US from AD, and the surety that the number of AD patients will greatly increase over the next 20–30 years, greater understanding of the molecular basis of pathogenesis and progression of AD is essential. Our laboratory is privileged to have contributed to better understanding of AD and provided rationales to identify effective therapeutic targets for this devastating dementing disorder. Show more

Keywords: Alzheimer’s disease, lipid peroxidation, neuronal death, oxidative stress, pathogenesis, predictions, progression, protein oxidation, redox proteomics

DOI: 10.3233/JAD-179912

Citation: Journal of Alzheimer's Disease, vol. 64, no. s1, pp. S469-S479, 2018

Authors: Butterfield, D. Allan | Sultana, Rukhsana

Article Type: Research Article

Abstract: Alzheimer disease is a common age-related neurodegenerative disease characterized pathologically by senile plaques, neurofibrillary tangles, synaptic disruption, and progressive neuronal deficits. The senile plaques contain amyloid-β (1–42) and amyloid-β (1–40), that has been shown by a number of laboratories to induce oxidative stress and as well as neurodegeneration, although the exact mechanisms remained to be defined. Our laboratory showed an increased oxidative stress in AD and MCI brain as indexed by protein oxidation and lipid peroxidation. In the present review, we summarize our finding of oxidatively modified proteins using a redox proteomics approach in AD and MCI brain to investigate …the mechanism that may be involved in MCI and AD pathogenesis and discuss our findings in terms of AD progression and pathogenesis. Show more

Keywords: Alzheimer's disease, mild cognitive impairment, oxidative stress, amyloid, redox proteomics

DOI: 10.3233/JAD-2007-12107

Citation: Journal of Alzheimer's Disease, vol. 12, no. 1, pp. 61-72, 2007

Authors: Sultana, Rukhsana | Butterfield, D. Allan

Article Type: Review Article

Abstract: Aging is the major risk factor associated with neurodegenerative diseases, including Alzheimer's disease (AD). Until now no clear understanding of the mechanisms of initiation and progression of this dementing disorder exists. Based on the studies that have been conducted so far amyloid β-peptide (Aβ), a protein found in senile plaques, one of the key pathological hallmarks of AD, has been reported to be critical in the pathogenesis of AD. Studies from our laboratory and others showed that Aβ can induce oxidative stress, which leads to oxidative modification of biomolecules, thereby diminishing the normal functions of neuronal cells and eventually leading …to loss of neurons and AD. In this review paper, we summarize evidence of oxidative stress in brains of AD and mild cognitive impairment patients, as well as the results from redox proteomics studies. The investigations have provided insights into the downstream effects of oxidative modification of key brain proteins in the pathogenesis of AD. Based on these redox proteomics results, we suggest future areas of research that could be considered to better understand this devastating dementing disorder. Show more

Keywords: Alzheimer's disease, lipid peroxidation, mild cognitive impairment, oxidative stress, protein carbonylation, protein nitration, redox proteomics

DOI: 10.3233/JAD-2012-129018

Citation: Journal of Alzheimer's Disease, vol. 33, no. s1, pp. S243-S251, 2013

Authors: Sultana, Rukhsana | Butterfield, D. Allan

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized pathologically by the presence of senile plaques, neurofibrillary tangles, and synapse loss. Increasing evidence supports a role of amyloid β-peptide (Aβ)-induced oxidative stress in the progression and pathogenesis of AD. In this review, we summarize evidence for a role of oxidative stress in the progression of AD by comparing the appearance of the same oxidized brain proteins from subjects with mild cognitive impairment (MCI), early AD (EAD), and late-stage AD, and relating these findings to the reported AD pathology. The identification of oxidized brain proteins in common in MCI, …EAD, and AD brain suggest that certain key pathways are triggered and may be involved in the progression of AD. Exploring these pathways in detail may provide clues for better understanding the pathogenesis and progression of AD and also for the development of effective therapies to treat or delay this dementing disorder. Show more

Keywords: Alzheimer's disease, amyloid, early Alzheimer's disease, mild cognitive impairment, oxidative stress, proteomics

DOI: 10.3233/JAD-2010-1222

Citation: Journal of Alzheimer's Disease, vol. 19, no. 1, pp. 341-353, 2010

Authors: Butterfield, D. Allan | Boyd-Kimball, Debra

Article Type: Review Article

Abstract: Oxidative stress is implicated in the pathogenesis and progression of Alzheimer’s disease (AD) and its earlier stage, amnestic mild cognitive impairment (aMCI). One source of oxidative stress in AD and aMCI brains is that associated with amyloid-β peptide, Aβ1-42 oligomers. Our laboratory first showed in AD elevated oxidative stress occurred in brain regions rich in Aβ1-42 , but not in Aβ1-42 -poor regions, and was among the first to demonstrate Aβ peptides led to lipid peroxidation (indexed by HNE) in AD and aMCI brains. Oxidatively modified proteins have decreased function and contribute to damaged key biochemical and metabolic pathways in …which these proteins normally play a role. Identification of oxidatively modified brain proteins by the methods of redox proteomics was pioneered in the Butterfield laboratory. Four recurring altered pathways secondary to oxidative damage in brain from persons with AD, aMCI, or Down syndrome with AD are interrelated and contribute to neuronal death. This “Quadrilateral of Neuronal Death” includes altered: glucose metabolism, mTOR activation, proteostasis network, and protein phosphorylation. Some of these pathways are altered even in brains of persons with preclinical AD. We opine that targeting these pathways pharmacologically and with lifestyle changes potentially may provide strategies to slow or perhaps one day, prevent, progression or development of this devastating dementing disorder. This invited review outlines both in vitro and in vivo studies from the Butterfield laboratory related to Aβ1-42 and AD and discusses the importance and implications of some of the major achievements of the Butterfield laboratory in AD research. Show more

Keywords: Alzheimer’s disease, amyloid beta-peptide 1–42, glucose metabolism, mTOR activation, oxidative stress, protein phosphorylation, proteostasis

DOI: 10.3233/JAD-170543

Citation: Journal of Alzheimer's Disease, vol. 62, no. 3, pp. 1345-1367, 2018

Authors: Butterfield, D. Allan | Griffin, Sue | Munch, Gerald | Pasinetti, Giulio Maria

Article Type: Research Article

Abstract: Alzheimer's disease (AD) brain is characterized by excess deposition of amyloid β-peptide (Aβ), particularly the 42-amino acid peptide [Aβ(1-42)] and by extensive oxidative stress. Several sources of the oxidative stress and inflammatory cascades are likely, including that induced by advanced glycation end products, microglial activation, and by Aβ(1-42) and its sequelae. This review briefly examines each of these sources of oxidative stress and inflammation in AD brain and discusses their potential roles in the clinical progression of AD dementia.

DOI: 10.3233/JAD-2002-4309

Citation: Journal of Alzheimer's Disease, vol. 4, no. 3, pp. 193-201, 2002

Authors: Yatin, Servet M. | Varadarajan, Sridhar | Butterfield, D. Allan

Article Type: Research Article

Abstract: Amyloid ß-peptide (Aß) is a 42-43 amino acid peptide known to accumulate in Alzheimer's disease (AD) brain. We previously reported that the neurotoxicity caused by Aß is a result of its associated free radicals, which can play an important role in generating oxidative stress. Aß(25-35)-associated oxidative stress-induced neuronal death in vitro is well established by many laboratories, including ours. However, the oxidative stress-induced by the full-length [Aß(1-42)] peptide is not well investigated. The protective effect of antioxidant vitamin E in full-length peptide-induced oxidative stress also has not been reported. Here, we report that the increased protein oxidation, reactive oxygen species …(ROS) formation, and neurotoxicity induced by Aß(1-42) in primary rat embryonic hippocampal neuronal culture are prevented by the free radical scavenger and antioxidant vitamin E. To test the hypothesis that vitamin E's protective effect may be due to inhibition of fibril formation, electron microscopy studies were undertaken. Vitamin E does not inhibit Aß(1-42) fibril formation, suggesting that the neuroprotection afforded by this molecule stems from other processes, most probably through the scavenging of Aß-associated free radicals. These results may have implications on the treatment of Alzheimer's disease. Show more

Keywords: Aß, amyloid ß-peptide, AD, Alzheimer's disease, APP, amyloid precursor protein, DCF-DA, dicholorofluorescin diacetate, DNPH, 2,4-dinitrophenylhydrazine, PBN, phenyl-a-tertbutyl-nitrone, ROS, reactive oxygen species, SP, senile plaques

DOI: 10.3233/JAD-2000-2212

Citation: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 123-131, 2000

Authors: Butterfield, D. Allan | Hardas, Sarita S. | Lange, Miranda L. Bader

Article Type: Review Article

Abstract: Recently, the oxidoreductase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has become a subject of interest as more and more studies reveal a surfeit of diverse GAPDH functions, extending beyond traditional aerobic metabolism of glucose. As a result of multiple isoforms and cellular locales, GAPDH is able to come in contact with a variety of small molecules, proteins, membranes, etc., that play important roles in normal and pathologic cell function. Specifically, GAPDH has been shown to interact with neurodegenerative disease-associated proteins, including the amyloid-β protein precursor (AβPP). Studies from our laboratory have shown significant inhibition of GAPDH dehydrogenase activity in Alzheimer's disease (AD) brain …due to oxidative modification. Although oxidative stress and damage is a common phenomenon in the AD brain, it would seem that inhibition of glycolytic enzyme activity is merely one avenue in which AD pathology affects neuronal cell development and survival, as oxidative modification can also impart a toxic gain-of-function to many proteins, including GAPDH. In this review, we examine the many functions of GAPDH with respect to AD brain; in particular, the apparent role(s) of GAPDH in AD-related apoptotic cell death is emphasized. Show more

Keywords: Alzheimer's disease, amyloid-β, amyloid-β protein precursor, apoptosis, glyceraldehyde-3-phosphate dehydrogenase, hypometabolism, oxidative stress

DOI: 10.3233/JAD-2010-1375

Citation: Journal of Alzheimer's Disease, vol. 20, no. 2, pp. 369-393, 2010

Authors: Sultana, Rukhsana | Mecocci, Patrizia | Mangialasche, Francesca | Cecchetti, Roberta | Baglioni, Mauro | Butterfield, D. Allan

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is histopathologically characterized by the presence of senile plaques, neurofibrillary tangles, and synapse loss. The main component of senile plaques is amyloid β-peptide (Aβ), which has been shown to induce oxidative stress in in vitro and in vivo studies. AD is associated with elevated levels of oxidative damage in brain and peripheral lymphocytes. Further Aβ has been found to be accumulated in mitochondria, which might contribute to the reported alterations in the mitochondrial morphology, and impaired mitochondrial energy metabolism in AD brain. Biomarkers are desperately needed for earlier diagnosis of AD and to monitor efficacy of new …therapies. Hence, in the present study we show that markers of oxidative damage are elevated in mitochondria isolated from AD lymphocytes suggesting that these oxidative stress indices potentially could serve as a viable biomarker for AD. Show more

Keywords: Alzheimer's disease, lymphocytes, mitochondria, 3-nitrotyrosine, oxidative stress, protein-bound 4 hydroxy-2 trans nonenal, protein carbonyls

DOI: 10.3233/JAD-2011-101425

Citation: Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 77-84, 2011