Proteasomal Dysfunction: A Common Feature of Neurodegenerative Diseases? Implications for the Environmental Origins of Neurodegeneration

Halliwell, Barry

doi:10.1089/ars.2006.8.2007

Cited by 40 publications

(35 citation statements)

References 170 publications

(163 reference statements)

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“…Oxidation modification of UCH-L1 has been observed in AD hippocampus (91,103) and PD (179). Mutations in this protein support the concept of impaired protein degradation, mitochondrial dysfunction, and proteasomal overload associated with many neurodegenerative disorders (181).…”

Section: Importance Of Clearance and Detoxification Systemsmentioning

confidence: 82%

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

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

156

142

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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: Importance Of Clearance and Detoxification Systemsmentioning

confidence: 82%

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

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

156

142

View full text Add to dashboard Cite

show abstract

“…Current research is uncovering several conditions that are proving to be commonalities among neurodegenerative diseases. These include protein aggregation, proteasomal or autophagic dysfunction, inflammation, neuronal apoptosis, oxidative stress, mitochondrial dysfunction, and interactions between neurons and glia (2,8,14,15,42,44,47,53,72). Although the causal nature of each of these conditions is often vigorously debated, their persistent presence and strong correlation with neuronal death warrants attempts to translate inhibitors of these processes to a therapeutic setting.…”

mentioning

confidence: 99%

The Nrf2/ARE Pathway as a Potential Therapeutic Target in Neurodegenerative Disease

Calkins

Johnson

Townsend

et al. 2009

Antioxidants & Redox Signaling

399

302

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Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce expression of a variety of cytoprotective and detoxification genes. Several of the genes commonly regulated by Nrf2 have been implicated in protection from neurodegenerative conditions. Work from several laboratories has uncovered the potential for Nrf2-mediated transcription to protect from neurodegeneration resulting from mechanisms involving oxidative stress. For this reason, Nrf2 may be considered a therapeutic target for conditions that are known to involve free radical damage. Because common mechanisms of neurodegeneration, such as mitochondrial dysfunction and build-up of reactive oxygen species, are currently being uncovered, targeting Nrf2 may be valuable in combating conditions with variable causes and etiologies. Most effectively to target this protein in neurodegenerative conditions, a description of the involvement of Nrf2 and potential for neuroprotection must come from laboratory models. Herein, we review the current literature that suggests that Nrf2 may be a valuable therapeutic target for neurodegenerative disease, as well as experiments that illustrate potential mechanisms of protection. Antioxid. Redox Signal. 11,[497][498][499][500][501][502][503][504][505][506][507][508]

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“…Indeed, many mutations associated with neurodegenerative disorders either generate proteins or peptides with a higher propensity to selfassemble, or they affect crucial functions for protein QC or the antioxidant defense. [5][6][7] Handling protein misfolding and oxidative stress is essential for all cells and the underlying mechanisms originated early in evolution. In fact, much of our understanding of these processes came from studies performed in the baker's yeast Saccharomyces cerevisiae.…”

mentioning

confidence: 99%

Yeast unfolds the road map toward α-synuclein-induced cell death

et al. 2009

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The budding yeast Saccharomyces cerevisiae has contributed significantly to our current understanding of eukaryotic cell biology. It served as a tool and model for unraveling the molecular basis of a wide variety of cellular phenomena, which seem to be conserved in other organisms. During the last decade, yeast has also extensively been used to study the mechanisms underlying several human diseases, including age-associated neurodegenerative disorders, such as Parkinson's, Huntington's and Alzheimer's disease. In this review, we focus on a yeast model for synucleinopathies and summarize recent studies that not only provided new clues on how the misfolding of a-synuclein (a-syn) triggers toxicity and eventually cell death, but that also led to the identification of conserved suppressor proteins, which are effective in protecting cells, including neurons, from the a-syn-induced cytotoxicity.

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Proteasomal Dysfunction: A Common Feature of Neurodegenerative Diseases? Implications for the Environmental Origins of Neurodegeneration

Cited by 40 publications

References 170 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

The Nrf2/ARE Pathway as a Potential Therapeutic Target in Neurodegenerative Disease

Yeast unfolds the road map toward α-synuclein-induced cell death

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