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Brain Oxidative Stress in the Pathogenesis and Progression of Alzheimer’s Disease

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Studies on Alzheimer's Disease

Abstract

Alzheimer’s disease is an age-related neurodegenerative disease and is characterized by the presence of senile plaques (SP), neurofibrillary tangles, and synapse loss. Amyloid-beta, one of the main components of SP, has been known to induce oxidative stress and is highly toxic. Using redox proteomics approaches a number of oxidatively modified proteins were identified in AD and mild cognitive impairment (MCI) brain that are consistent with the clinical presentation, pathology, and biochemistry. The identification of key proteins that are highly susceptible to amyloid-beta-mediated oxidation might serve as biomarkers for use in diagnosing and also in the identification of therapeutic targets to prevent or delay this devastating disorder.

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Abbreviations

3-NT:

3-nitro tyrosine

AD:

Alzheimer’s disease

ADDL:

β-amyloid-derived-diffusible ligands

AGEs:

Advance glycation end products

AICD:

APPs intracellular c-terminal domain

APC:

Anaphase promoting complex

APOE 4 :

Apolipoprotein E allele 4

APP:

Amyloid precursor protein

Aβ:

Amyloid beta-peptide

AβPP:

β-amyloid precursor protein

BR:

Bilirubin-IX-alpha

BRCA 1:

Breast cancer type-1 susceptibility protein

BV:

Biliverdin-IX-alpha

BVR-A:

Biliverdin reductase-A

CBP:

Creb response binding protein

CDKs:

Cyclin-dependent kinases

CEL:

N-carboxyethyl-lysine

CML:

Nε-(carboxymethyl) lysine

c-MYC:

Cellular-myelocytomatosis

CR:

Carbonyl reductase

CSF:

Cerebral spinal fluid

DMDMAH-1:

Dimethylarginine dimethylaminohydrolase 1

DRP-2:

Dihydropyrimidinase-related protein 2

EOAD:

Early onset-AD

F2-IsoP:

F2-isoprostane

F4-NP:

F4-Neuroprostane

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

Glycer-AGE:

Glyceraldehyde-derived AGEs

GPX:

Glutathione peroxidase

GRD:

Glutathione reductase

GRP:

Glucose regulated protein precursor

GSH:

Glutathione

GSK3β:

Glycogen synthase kinase 3-β

GST M:

Glutathione-S-transferase Mu

HNE:

4-hydroxy 2-trans-nonenal

HNE-GSH:

HNE-glutathione

HO-1:

Heme oxygenase-1

HO-2:

Heme oxygenase-2

HSPA8:

Heat shock protein A8

iASPP:

Inhibitor of apoptosis-stimulating protein of p53 (iASPP)

IDE:

Insulin degrading enzyme

IGF-1:

Insulin growth factor-1 (IGF-1)

IKKβ:

IkB kinase type β

iNOS:

Inducible nitric oxide synthase

IPL:

Inferior parietal lobule

LDH:

Lactate dehydrogenase

LOAD:

Late onset-AD

MAPK:

Mitogen-activated protein kinase

MCI/aMCI:

Non-amnestic/amnestic mild-cognitive impairment

MDA:

Malondialdehyde

MDH:

Malate dehydrogenase 1 (MDH)

Mdm-2:

Murine double minute-2

MMSE:

Mini-mental state examination

MnSOD:

Manganese superoxide dismutase

MRP3:

Multidrug resistant protein-3

mtDNA:

Mitochondrial DNA

nDNA:

Nuclear DNA

NF-E2:

Nuclear factor-erythroid 2

NFT:

Neurofibrillary tangles

NF-κB:

Nuclear factor kappa-B

NINCDS-ADRDA:

National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association

NMDA:

N-methyl-d-aspartate

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NPrG:

1-N2-propanodeoxyguanosine

Nrf-2:

Nuclear factor related factor 2

PDI:

Protein disulfide isomerase

PICALM:

Phosphatidylinositol-binding clathrin assembly protein

Pin1:

Peptidyl prolyl cis-trans isomerase

PLK:

Polo-like kinase

PP2A:

Protein phosphatase 2-A

PPIase:

Peptidyl-prolyl cis/trans isomerase

PRVI:

Peroxiredoxin 6

PS-1:

Presenilin-1

PS-2:

presenilin-2

Rb:

Retinoblastoma protein

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

rRNA:

Ribosomal RNA

RSNO:

S-nitrosothiols

SBP1:

Syntaxin binding protein I

SCFskp2 :

Skp cullin, F-box containing complex

SOD:

Superoxide dismutase

SOD1/SOD2:

Superoxide dismutase1/2

Thio-1:

Thioredoxin-1

TNF-α:

Tumor necrosis factor-α

TPI:

Triose phosphate isomerase (TPI)

tRNA:

transfer RNA

UCH l-1:

Ubiquitin carboxy-terminal hydrolase l-1

UPR:

Unfolded protein response

VDAC:

Voltage-dependent anion channel

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Authors and Affiliations

  1. Department of Chemistry, Center of Membrane Sciences, The Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40506-0055, USA

    Rukhsana Sultana Ph.D., Aaron M. Swomley Ph.D. & D. Allan Butterfield Ph.D.

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  1. Rukhsana Sultana Ph.D.
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  2. Aaron M. Swomley Ph.D.
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  3. D. Allan Butterfield Ph.D.
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Correspondence to D. Allan Butterfield Ph.D. .

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Editors and Affiliations

  1. Pharmacology, Temple University, Philadelphia, Pennsylvania, USA

    Domenico Praticὸ

  2. Istituto di Gerontologia e Geriatria, Università degli Studi di Perugia, Perugia, Italy

    Patrizia Mecocci

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Sultana, R., Swomley, A.M., Butterfield, D.A. (2013). Brain Oxidative Stress in the Pathogenesis and Progression of Alzheimer’s Disease. In: Praticὸ, D., Mecocci, P. (eds) Studies on Alzheimer's Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-598-9_8

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