Isomerization of Asp7 leads to increased toxic effect of amyloid-β42 on human neuronal cells

Mitkevich, Vladimir A.; Petrushanko, Irina Yu.; Yegorov, Yegor E.; Simonenko, O V; Vishnyakova, Khava S.; Kulikova, Alexandra A.; Tsvetkov, P O; Makarov, Alexander А.; Kozin, Sergey A.

doi:10.1038/cddis.2013.492

Cited by 57 publications

(44 citation statements)

References 7 publications

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“…Even though isoD7-Aβ42 and Aβ42 have practically the same capacity for spontaneous aggregation in vitro (Fukuda et al, 1999; Kozin et al, 2013), isoD7-Aβ42 is much more toxic for neuronal cells than the intact Aβ42 (Mitkevich et al, 2013). The metal-binding domain of isoD7-Aβ42 was earlier shown to be extremely susceptible to zinc-induced oligomerization (Tsvetkov et al, 2008; Istrate et al, 2016), which strongly supports the importance of this process in AD cerebral β-amyloidosis (Kulikova et al, 2015; Kozin et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Intravenously Injected Amyloid-β Peptide With Isomerized Asp7 and Phosphorylated Ser8 Residues Inhibits Cerebral β-Amyloidosis in AβPP/PS1 Transgenic Mice Model of Alzheimer’s Disease

et al. 2018

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Cerebral β-amyloidosis, an accumulation in the patient’s brain of aggregated amyloid-β (Aβ) peptides abnormally saturated by divalent biometal ions, is one of the hallmarks of Alzheimer’s disease (AD). Earlier, we found that exogenously administrated synthetic Aβ with isomerized Asp7 (isoD7-Aβ) induces Aβ fibrillar aggregation in the transgenic mice model of AD. IsoD7-Aβ molecules have been implied to act as seeds enforcing endogenous Aβ to undergo pathological aggregation through zinc-mediated interactions. On the basis of our findings on zinc-induced oligomerization of the metal-binding domain of various Aβ species, we hypothesize that upon phosphorylation of Ser8, isoD7-Aβ loses its ability to form zinc-bound oligomeric seeds. In this work, we found that (i) in vitro isoD7-Aβ with phosphorylated Ser8 (isoD7-pS8-Aβ) is less prone to spontaneous and zinc-induced aggregation in comparison with isoD7-Aβ and intact Aβ as shown by thioflavin T fluorimetry and dynamic light scattering data, and (ii) intravenous injections of isoD7-pS8-Aβ significantly slow down the progression of institutional β-amyloidosis in AβPP/PS1 transgenic mice as shown by the reduction of the congophilic amyloid plaques’ number in the hippocampus. The results support the role of the zinc-mediated oligomerization of Aβ species in the modulation of cerebral β-amyloidosis and demonstrate that isoD7-pS8-Aβ can serve as a potential molecular tool to block the aggregation of endogenous Aβ in AD.

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Section: Introductionmentioning

confidence: 99%

Intravenously Injected Amyloid-β Peptide With Isomerized Asp7 and Phosphorylated Ser8 Residues Inhibits Cerebral β-Amyloidosis in AβPP/PS1 Transgenic Mice Model of Alzheimer’s Disease

et al. 2018

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“…Большинство исследований в этой области сфокусировано на роли бета-амилоидного пептида в формировании внеклеточных амилоидных бляшек и белковых агрегатов, а также механизмах их токсичности (напр. [3][4][5][6]). Однако становится всё более очевидным, что бета-амилоидный пептид может накапливаться внутри нейронов и взаимодействовать с внутриклеточными белкамимишенями [1,7,8], причём внутриклеточные события, по-видимому, предшествуют образованию внеклеточных олигомеров/агрегатов бета-амилоидного пептида [7,8].…”

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The effect of neuroprotector isatin on binding of some model proteins with beta-amyloid peptide: a biosensor study

et al. 2016

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The amyloid-beta peptide 1-42 formed during proteolytic processing of the amyloid precursor protein (APP) plays a key role in the development or progression of Alzheimer's disease (AD) and other pathologies associated with formation of protein aggregates in the central nervous system. Recent proteomic profiling of mouse and rat brain preparations by means of beta-amyloid peptide immobilized on Affigel-10 revealed a large group of amyloid-binding proteins (n>80). Many (about 25%) of these proteins were previously identified as isatin-binding proteins. The aim of this study was to validate direct interaction between beta-amyloid peptide and highly purified intact and oxidized peroxiredoxin, M-type pyruvate kinase, alpha-enolase, and the effect of isatin on this interaction. The study performed using SPR-based Biacore 3000 and Biacore X100 biosensors has shown that all the proteins form molecular complexes with immobilized beta-amyloid peptide. The Kd values for these complexes varied from 8.36х10-8 M (peroxiredoxin) to 1.97х10-6 M (alpha-enolase). Oxidative modification of investigated proteins caused opposite effects on complexes of these peptides with beta-amyloid. The endogenous neuroprotector isatin increased dissociation of complexes formed by beta-amyloid peptide with both intact proteins (peroxiredoxin, glyceraldehyde-3-phosphate dehydrogenase) and/or oxidized proteins (peroxiredoxin, pyruvate kinase) used in this study.

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“…The amyloid-β peptide 1 – 42 formed during proteolytic processing of the amyloid precursor protein (APP) is considered as a key player in the development or progression of Alzheimer’s disease (AD) and other pathologies associated with the formation of protein aggregates in the central nervous system ([ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ] and many others). Although much attention is paid to formation of extracellular amyloid plaques and protein aggregates as well as to corresponding mechanisms of their toxicity, good evidence exists that intracellular amyloid-β can accumulate intraneuronally and contribute to disease progression [ 4 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Endogenous Non-Peptide Molecule Isatin and Hydrogen Peroxide on Proteomic Profiling of Rat Brain Amyloid-β Binding Proteins: Relevance to Alzheimer’s Disease?

Медведев

Buneeva

Kopylov

et al. 2014

IJMS

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The amyloid-β peptide is considered as a key player in the development and progression of Alzheimer’s disease (AD). Although good evidence exists that amyloid-β accumulates inside cells, intracellular brain amyloid-binding proteins remain poorly characterized. Proteomic profiling of rat brain homogenates, performed in this study, resulted in identification of 89 individual intracellular amyloid-binding proteins, and approximately 25% of them were proteins that we had previously identified as specifically binding to isatin, an endogenous neuroprotector molecule. A significant proportion of the amyloid-binding proteins (more than 30%) are differentially expressed or altered/oxidatively modified in AD patients. Incubation of brain homogenates with 70 µM hydrogen peroxide significantly influenced the profile of amyloid-β binding proteins and 0.1 mM isatin decreased the number of identified amyloid-β binding proteins both in control and hydrogen peroxide treated brain homogenates. The effects of hydrogen peroxide and isatin have been confirmed in optical biosensor experiments with purified glyceraldehyde-3-phosphate dehydrogenase, one of the known crucial amyloid-β binding proteins (also identified in this study). Data obtained suggest that isatin protects crucial intracellular protein targets against amyloid binding, and possibly favors intracellular degradation of this protein via preventing formation of amyloid-β oligomers described in the literature for some isatin derivatives.

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Isomerization of Asp7 leads to increased toxic effect of amyloid-β42 on human neuronal cells

Cited by 57 publications

References 7 publications

Intravenously Injected Amyloid-β Peptide With Isomerized Asp7 and Phosphorylated Ser8 Residues Inhibits Cerebral β-Amyloidosis in AβPP/PS1 Transgenic Mice Model of Alzheimer’s Disease

Intravenously Injected Amyloid-β Peptide With Isomerized Asp7 and Phosphorylated Ser8 Residues Inhibits Cerebral β-Amyloidosis in AβPP/PS1 Transgenic Mice Model of Alzheimer’s Disease

The effect of neuroprotector isatin on binding of some model proteins with beta-amyloid peptide: a biosensor study

The Effects of Endogenous Non-Peptide Molecule Isatin and Hydrogen Peroxide on Proteomic Profiling of Rat Brain Amyloid-β Binding Proteins: Relevance to Alzheimer’s Disease?

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