Identification of new modulators and protein alterations in non‐apoptotic programmed cell death

Sperandio, Sabina; Poksay, Karen S.; Schilling, Birgit; Crippen, Danielle; Gibson, Bradford W.; Bredesen, Dale E.

doi:10.1002/jcb.22870

Cited by 62 publications

(69 citation statements)

References 32 publications

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“…Apoptosis is initiated when phosphatidylserine resides on the outer leaflet of the membrane. Loss of function and changes in conformation of PEBP conceivably could lead to loss of phospholipid asymmetry, a signal for neuronal apoptosis, which further supports the role of PEBP as a parapoptosis inhibitor (191). HNE modification of PEBP may impact lipid asymmetry as loss of activity is observed in AD and MCI and mouse models of familial AD (13,14,80) and can potentially disrupt cellular homeostasis.…”

Section: Energy Dysfunction: Atp Synthase and A-enolasementioning

confidence: 74%

4-Hydroxy-2-Nonenal, a Reactive Product of Lipid Peroxidation, and Neurodegenerative Diseases: A Toxic Combination Illuminated by Redox Proteomics Studies

Perluigi

Coccia

Butterfield

2012

Antioxidants & Redox Signaling

185

133

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Significance: Among different forms of oxidative stress, lipid peroxidation comprises the interaction of free radicals with polyunsaturated fatty acids, which in turn leads to the formation of highly reactive electrophilic aldehydes. Among these, the most abundant aldehydes are 4-hydroxy-2-nonenal (HNE) and malondialdehyde, while acrolein is the most reactive. HNE is considered a robust marker of oxidative stress and a toxic compound for several cell types. Proteins are particularly susceptible to modification caused by HNE, and adduct formation plays a critical role in multiple cellular processes. Recent Advances: With the outstanding progress of proteomics, the identification of putative biomarkers for neurodegenerative disorders has been the main focus of several studies and will continue to be a difficult task. Critical Issues: The present review focuses on the role of lipid peroxidation, particularly of HNE-induced protein modification, in neurodegenerative diseases. By comparing results obtained in different neurodegenerative diseases, it may be possible to identify both similarities and specific differences in addition to better characterize selective neurodegenerative phenomena associated with protein dysfunction. Results obtained in our laboratory and others support the common deregulation of energy metabolism and mitochondrial function in neurodegeneration. Future Directions: Research towards a better understanding of the molecular mechanisms involved in neurodegeneration together with identification of specific targets of oxidative damage is urgently required. Redox proteomics will contribute to broaden the knowledge in regard to potential biomarkers for disease diagnosis and may also provide insight into damaged metabolic networks and potential targets for modulation of disease progression. Antioxid. Redox Signal. 17, 1590-1609.

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Section: Energy Dysfunction: Atp Synthase and A-enolasementioning

confidence: 74%

4-Hydroxy-2-Nonenal, a Reactive Product of Lipid Peroxidation, and Neurodegenerative Diseases: A Toxic Combination Illuminated by Redox Proteomics Studies

Perluigi

Coccia

Butterfield

2012

Antioxidants & Redox Signaling

185

133

View full text Add to dashboard Cite

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“…Apoptosis is initiated when phosphatidylserine resides on the outer leaflet of the membrane. Loss of function and changes in conformation of PEBP conceivably could lead to loss of phospholipid asymmetry, a signal for neuronal apoptosis, which further supports the role of PEBP as a parapoptosis inhibitor (359). Loss of PEBP may impact lipid asymmetry, as loss of activity is observed in AD and MCI and mouse models of familial AD (23,24,166) and can potentially disrupt cellular homeostasis.…”

Section: Ead Carbonylated Proteinsmentioning

confidence: 75%

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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“…23 Paraptosis is a recently discovered form of non-apoptotic cell death, which is distinguished from apoptosis by the absence of apoptotic morphology, DNA fragmentation or caspase activation. 24 Glioblastoma cells are characterized by resistance to apoptosis, which is largely responsible for the low effectiveness of classical chemotherapeutic approaches, most of which are based on apoptosis induction. Thus, ophiobolin A is an agent with a novel mode of action (MOA) capable of overcoming apoptosis resistance in glioblastoma.…”

Section: Paal–knorr Modifications Of Biological Targets With Naturamentioning

confidence: 99%

Covalent modification of biological targets with natural products through Paal–Knorr pyrrole formation

Kornienko

Clair

2017

Nat. Prod. Rep.

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Natural products and endogenous metabolites engage specific targets within tissues and cells through complex mechanisms. This review examines the extent to which natural systems have adopted the Paal–Knorr reaction to engage nucleophilic amine groups within biological targets. Current understanding of this mode of reactivity is limited by only a few examples of this reaction in a biological context. This highlight is intended to stimulate the scientific community to identify potential research directions and applications of the Paal–Knorr reaction in native and engineered biological systems.

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Identification of new modulators and protein alterations in non‐apoptotic programmed cell death

Cited by 62 publications

References 32 publications

4-Hydroxy-2-Nonenal, a Reactive Product of Lipid Peroxidation, and Neurodegenerative Diseases: A Toxic Combination Illuminated by Redox Proteomics Studies

4-Hydroxy-2-Nonenal, a Reactive Product of Lipid Peroxidation, and Neurodegenerative Diseases: A Toxic Combination Illuminated by Redox Proteomics Studies

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

Covalent modification of biological targets with natural products through Paal–Knorr pyrrole formation

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