Proteomics Analysis of the Alzheimer's Disease Hippocampal Proteome

Sultana, Rukhsana; Boyd‐Kimball, Debra; Cai, Janet; Pierce, William M.; Klein, Jon B.; Merchant, Michael L.; Butterfield, D. Allan

doi:10.3233/jad-2007-11203

Cited by 211 publications

(169 citation statements)

References 79 publications

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“…Due to its involvement in glycolytic pathway, carbonylation, and reported decreased expression and activity of PGM1 in the AD brain compared with the age-matched controls are consistent with the loss of total cellular energetics in AD (362). Taken together, oxidative inactivation of these ATP-related enzymes may be related to known metabolic defects in AD detected by PET scanning (309,317).…”

Section: Identification Of Carbonylated Proteins In Brainsupporting

confidence: 53%

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

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153

134

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Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidativestress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610-1655.

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Section: Identification Of Carbonylated Proteins In Brainsupporting

confidence: 53%

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

Self Cite

153

134

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“…The overall increase in ferritin seems to exceed that of iron, at least in the hippocampus of AD patients, hence most iron should be ferritin-bound (Galazka-Friedman et al 2004), thus in a safe state. Interestingly a quantitative analyses of isoferritins in the brain of controls and AD patients found region and disease specific alteration of the balance between H and L subunits, with the L subunit concentration being lower in the cortex and in the SN of AD brain (Connor et al 1995); a proteomic analysis of AD hippocampi also found elevated H-chain levels (Sultana et al 2007). As observed in different experimental systems, this imbalance could be associated with an abnormal iron management by ferritin itself.…”

Section: Ferritin In Brain Disorders With Altered Iron Homeostasismentioning

confidence: 90%

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

2014

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Iron is an abundant transition metal that is essential for life, being associated to many enzyme and oxygen carrier proteins involved in a variety of fundamental cellular processes. At the same time the metal is potentially toxic due to its capacity to engage in the catalytic production of noxious reactive oxygen species. The control of iron availability in the cells is largely dependent on ferritins, ubiquitous proteins with storage and detoxification capacity. In mammals, cytosolic ferritins are composed of two types of subunits, the H and the L chain, assembled to form a 24-mer spherical cage. Ferritin is present also in mitochondria, in the form of a complex with 24 identical chains. Even though the proteins have been known for a long time, their study is a very active and interesting field yet. In this review we will focus our attention to mammalian cytosolic and mitochondrial ferritins, describing the most recent advancement regarding their storage and antioxidant function, the effects of their genetic mutations in human pathology, and also the possible involvement in non-iron related activities. We will also discuss recent evidence connecting ferritins and the toxicity of iron in a set of neurodegenerative disorder characterized by focal cerebral siderosis. IntroductionThe adaptation of life to an oxic environment required the development of mechanisms to deal with the transformation of the water soluble ferrous ion (Fe 2+ ) to the insoluble ferric ion (Fe 3+ ) and with the concomitant generation of dangerous reactive oxygen species (ROS). The ferritin molecules represent an important and ancient mean developed by organisms in the three domains of life to safely handle the necessary, yet potentially toxic metal. Their ability to detoxify and store the metal through safe oxidation processes protects the cells from undue iron-dependent redox chemistry, while a controlled release of the metal guarantees its availability for different and essential enzymatic reactions. Storage and detoxification of iron represent the main functions of these molecules, and much work has been done to understand the chemical and molecular details of this

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“…We, and others, have also demonstrated the potential for this approach in identifying neurodegenerative-specific changes in postmortem brain tissues. Using subproteome studies, constituents of isolated amyloid plaques (18), AD hippocampus (19), cortical Lewy bodies (20), AD membrane fraction (21), and specific phosphorylation sites in neurofibrillary tangles (22) were identified. Using broader discovery proteomics, we demonstrated unique candidate proteins in both AD (23,24) and FTLD-U (25).…”

mentioning

confidence: 99%

U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer’s disease

Bai

Hales

Chen³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

274

362

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Deposition of insoluble protein aggregates is a hallmark of neurodegenerative diseases. The universal presence of β-amyloid and tau in Alzheimer's disease (AD) has facilitated advancement of the amyloid cascade and tau hypotheses that have dominated AD pathogenesis research and therapeutic development. However, the underlying etiology of the disease remains to be fully elucidated. Here we report a comprehensive study of the human brain-insoluble proteome in AD by mass spectrometry. We identify 4,216 proteins, among which 36 proteins accumulate in the disease, including U1-70K and other U1 small nuclear ribonucleoprotein (U1 snRNP) spliceosome components. Similar accumulations in mild cognitive impairment cases indicate that spliceosome changes occur in early stages of AD. Multiple U1 snRNP subunits form cytoplasmic tangle-like structures in AD but not in other examined neurodegenerative disorders, including Parkinson disease and frontotemporal lobar degeneration. Comparison of RNA from AD and control brains reveals dysregulated RNA processing with accumulation of unspliced RNA species in AD, including myc boxdependent-interacting protein 1, clusterin, and presenilin-1. U1-70K knockdown or antisense oligonucleotide inhibition of U1 snRNP increases the protein level of amyloid precursor protein.Thus, our results demonstrate unique U1 snRNP pathology and implicate abnormal RNA splicing in AD pathogenesis.proteomics | liquid chromatography-tandem mass spectrometry | U1A | RNA-seq | premature cleavage and polyadenylation

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Proteomics Analysis of the Alzheimer's Disease Hippocampal Proteome

Cited by 211 publications

References 79 publications

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration

U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in Alzheimer’s disease

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