Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment

Butterfield, D. Allan; Reed, Tanea T.; Newman, Shelley F.; Sultana, Rukhsana

doi:10.1016/j.freeradbiomed.2007.05.037

Cited by 508 publications

(391 citation statements)

References 269 publications

(425 reference statements)

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“…At this time cells were treated with 10 M A␤ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Cells were harvested in 2% SDS buffer as described above at 4,8,12,16,24,36, and 48 h post-A␤ treatment. PDK1 and LDHA were visualized by Western blot analysis as described above, and protein quantification was performed using ImageJ software.…”

Section: Methodsmentioning

confidence: 99%

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Overexpression of Pyruvate Dehydrogenase Kinase 1 and Lactate Dehydrogenase A in Nerve Cells Confers Resistance to Amyloid β and Other Toxins by Decreasing Mitochondrial Respiration and Reactive Oxygen Species Production

Newington

Rappon

Albers³

et al. 2012

Journal of Biological Chemistry

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Background: Aerobic glycolysis promotes resistance against A␤ toxicity. Results: Increased LDHA and PDK1 expression attenuates mitochondrial activity and confers resistance to A␤. These proteins are down-regulated in a transgenic Alzheimer disease (AD) mouse model, and PDK1 is decreased in AD brain. Conclusion: PDK and LDHA are central mediators of A␤ resistance. Significance: Drugs that augment aerobic glycolysis may enhance brain cell survival in AD patients.

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Section: Methodsmentioning

confidence: 99%

“…Overall, cellular ROS levels have been previously shown to increase when cells are treated with stressors such as A␤ (6,8). We therefore sought to examine if the cellular levels of ROS were altered in B12 cells overexpressing LDHA or PDK1.…”

Section: Overexpression Of Ldha or Pdk1 Decreases Oxygen Consumption mentioning

confidence: 99%

Overexpression of Pyruvate Dehydrogenase Kinase 1 and Lactate Dehydrogenase A in Nerve Cells Confers Resistance to Amyloid β and Other Toxins by Decreasing Mitochondrial Respiration and Reactive Oxygen Species Production

Newington

Rappon

Albers³

et al. 2012

Journal of Biological Chemistry

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“…Their results have focused on about 15 proteins that have broad cellular functions and are distributed across several different organelles or cellular compartments. This work has been reviewed recently in this journal [92]. Notably, there is at least partial overlap in the oxidized proteins identified by this approach in tissue from patients with MCI or LOAD.…”

Section: Autopsymentioning

confidence: 98%

Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models

Sonnen¹,

Breitner²,

Lovell³

et al. 2008

Free Radical Biology and Medicine

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“…For example, although it is known that alterations in redox homeostasis contribute to the pathogenesis of disorders like Parkinson's disease, Alzheimer's disease and Huntington's disease, basic questions -such as whether the principal targets of oxidation are neurons or glial cells -remain unanswered [12,13]. Current spectrophotometric and proteomic techniques rely upon sub-cellular fractionation of total tissue homogenates.…”

mentioning

confidence: 99%

A FRET-based method to study protein thiol oxidation in histological preparations

Mastroberardino

Orr

et al. 2008

Free Radical Biology and Medicine

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Cysteine residues in proteins have important biological roles. For example, disulfides bonds are important structural elements; additionally, reversible oxidation of thiols to disulfides functions as a molecular switch and constitutes an early response to oxidative damage Because organs are heterogeneous structures composed of diverse cell types, there is a compelling need for a histological approach to investigate thiol oxidation in situ in order to address the role of specific cell types in oxidative imbalance. Here we describe a fluorescence technique -which can be used in association with standard immunological staining procedures -to detect variations in disulfides in histological preparations. Moreover, by monitoring the fluorescence resonance energy transfer (FRET) between a labeled specific primary antibody and the thiol probe described here, this method can detect thiol oxidation in candidate proteins of interest. When applied to an animal model of Parkinson's disease, our technique demonstrated that thiol oxidation occurs selectively in the dopaminergic neurons of the substantia nigra, the same neurons that are lost selectively in the disease. In summary, this technique provides a new, powerful tool to provide further understanding of oxidative imbalance, a phenomenon common to many diseases. Keywords fluorescence microscopy; FRET; oxidative stress; cysteine; thiols; disulfides; Parkinson's disease Thiols are the functional groups in the side chain of the amino acid, cysteine. Depending upon the oxido-reductive (redox) status of the surrounding environment, thiols exist either in the reduced form of free thiols (-SH) or oxidized to disulfides (-S-S-). Disulfides are well known to play an important structural role, contributing to the maintenance of the proper folding in proteins. More recently it was found that the formation of disulfides in proteins also exerts critical regulatory functions: vital mechanisms such as protein import, regulation of signal transduction cascades, regulation of the activity of transcription factors and proper function of the mitochondrial electron transport system rely on disulfide oxidation or reduction [1][2][3][4]. Moreover, the formation of disulfides represents an early, reversible response to oxidative *Corresponding author: mastroberardinopg@upmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Increasing interest in the study of thiols has led to the development of a variety of technical approaches to detect thiols and disulfides. In particular, several spectrophotometry-based protocols were developed to measure t...

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Roles of amyloid β-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment

Cited by 508 publications

References 269 publications

Overexpression of Pyruvate Dehydrogenase Kinase 1 and Lactate Dehydrogenase A in Nerve Cells Confers Resistance to Amyloid β and Other Toxins by Decreasing Mitochondrial Respiration and Reactive Oxygen Species Production

Overexpression of Pyruvate Dehydrogenase Kinase 1 and Lactate Dehydrogenase A in Nerve Cells Confers Resistance to Amyloid β and Other Toxins by Decreasing Mitochondrial Respiration and Reactive Oxygen Species Production

Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models

A FRET-based method to study protein thiol oxidation in histological preparations

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