Clusterin (apoJ) Alters the Aggregation of Amyloid β-Peptide (Aβ1-42) and Forms Slowly Sedimenting Aβ Complexes That Cause Oxidative Stress

Oda, Tsukasa; Wals, P.A.; Hh, Osterburg; Sa, Johnson; Pasinetti, Giulio Maria; Morgan, Tomos E.; Rozovsky, Irina; Wb, Stine; Snyder, Seth W.; Tf, Holzman

doi:10.1006/exnr.1995.1080

Cited by 342 publications

(233 citation statements)

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“…Recent evidence strongly suggests that soluble protofibril species are the pathogenic agents in amyloid diseases [29,30]. In cell culture experiments in the presence of clusterin, conflicting results were obtained with clusterin enhancing oxidative stress caused by A in [27] but being protective under the conditions used in [28]. Our in vitro studies have shown that fibril formation by apolipoprotein C-II (apoC-II) is potently inhibited by clusterin and -crystallin [16,31].…”

Section: Parallels Between the Structure And Mechanism Of Chaperone Amentioning

confidence: 97%

“…Thus, under fibril-forming conditions it will be ascertained whether clusterin and sHsps over-expression is deleterious to cell viability due to their potentiation of neurotoxicity via stabilization of intermediately-folded protofibril species, as has been implied from in vitro and cell culture studies [26,27]. The role of individual chaperones, and their possible synergistic interactions, in the modulation of fibril formation will also become much clearer.…”

Section: Unanswered Questions and Directions For Shsp And Clusterin Rmentioning

confidence: 99%

“…In vitro, B-crystallin and clusterin have both been found to inhibit amyloid fibril formation, e.g. by the amyloid -peptide (A), the putative causative agent in Alzheimer's disease [26][27][28]. However, in cell culture experiments, A-crystallin enhanced A  neurotoxicity, possibly by stabilizing the small soluble protofibril species (Fig.…”

Section: Parallels Between the Structure And Mechanism Of Chaperone Amentioning

confidence: 99%

“…The diagram represents the interaction of sHsps and clusterin with amorphously aggregating target proteins. When interacting with amyloid fibril-forming target proteins (under slowly aggregating conditions), complexation may not occur; instead, the partially folded protofibril species is stabilized and large-scale aggregation is prevented [16,[26][27][28]31].…”

Section: Unanswered Questions and Directions For Shsp And Clusterin Rmentioning

confidence: 99%

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Small Heat‐shock Proteins and Clusterin: Intra‐ and Extracellular Molecular Chaperones with a Common Mechanism of Action and Function?

et al. 2003

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Small heat-shock proteins (sHsps) and clusterin are molecular chaperones that share many functional similarities despite their lack of significant sequence similarity. These functional similarities, and some differences, are discussed. sHsps are ubiquitous intracellular proteins whereas clusterin is generally found extracellularly. Both chaperones potently prevent the amorphous aggregation and precipitation of target proteins under stress conditions such as elevated temperature, reduction and oxidation. In doing so, they act on the slow off-folding protein pathway. The conformational dynamism and aggregated state of both proteins may be crucial for their chaperone function. Subunit exchange is likely to be important in regulating chaperone action; the dissociated form of the protein is probably the chaperone-active species rather than the aggregated state. They both exert their chaperone action without the need for hydrolysis of ATP and have little ability to refold target proteins. Increased expression of sHsp and clusterin accompanies a range of diseases, e.g. Alzheimer's, Creutzfeldt-Jakob and Parkinson's diseases, that arise from protein misfolding and deposition of highly structured protein aggregates known as amyloid fibrils. The interaction of sHsps and clusterin with fibril-forming species is discussed along with their ability to prevent fibril formation, probably via utilization of their chaperone ability. Disciplines Life Sciences | Physical Sciences and Mathematics | Social and Behavioral Sciences Publication DetailsThis article was originally published as Carver, JA, Rekas, A, Thorn, DC and Wilson, MR, Small heat-shock proteins and clusterin: intra-and extracellular molecular chaperones with a common mechanism of action and function, IUBMB Life, 55, 2003, 661-668 AbstractSmall heat-shock proteins (sHsps) and clusterin are molecular chaperones that share many functional similarities despite their lack of significant sequence similarity. These functional similarities, and some differences, are discussed. sHsps are ubiquitous intracellular proteins whereas clusterin is generally found extracellularly. Both chaperones potently prevent the amorphous aggregation and precipitation of target proteins under stress conditions such as elevated temperature, reduction and oxidation. In doing so, they act on the slow off-folding protein pathway. The conformational dynamism and aggregated state of both proteins may be crucial for their chaperone function. Subunit exchange is likely to be important in regulating chaperone action; the dissociated form of the protein is probably the chaperone-active species rather than the aggregated state. They both exert their chaperone action without the need for hydrolysis of ATP and have little ability to refold target proteins. Increased expression of sHsp and clusterin accompanies a range of diseases, e.g. Alzheimer's, Creutzfeldt-Jakob and Parkinson's diseases, that arise from protein misfolding and deposition of highly structured protein aggregates known as amyloid f...

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Section: Parallels Between the Structure And Mechanism Of Chaperone Amentioning

confidence: 97%

Section: Unanswered Questions and Directions For Shsp And Clusterin Rmentioning

confidence: 99%

Section: Parallels Between the Structure And Mechanism Of Chaperone Amentioning

confidence: 99%

Section: Unanswered Questions and Directions For Shsp And Clusterin Rmentioning

confidence: 99%

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Small Heat‐shock Proteins and Clusterin: Intra‐ and Extracellular Molecular Chaperones with a Common Mechanism of Action and Function?

et al. 2003

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“…Under this hypothesis, single Aβ proteins (monomers) form into units of two (dimers), three (trimers), four (tetramers), or more molecules. Oda and colleagues [18] advanced the concept of soluble small soluble Aβ and Lambert and others demonstrated they could be formed from synthetic Aβ [11,12]. Walsh and colleagues showed that Chinese hamster ovary cells (CHO) when over-expressing a human mutant form of APP secrete Aβ oligomers in the culture medium [35].…”

mentioning

confidence: 99%

Oligomers of the amyloid-β protein disrupt working memory: Confirmation with two behavioral procedures

Poling

Morgan-Paisley

Panos

et al. 2008

Behavioural Brain Research

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Converging lines of evidence suggest that oligomers of amyloid-β play a role in the cognitive impairment characteristic of Alzheimer's disease, but only three studies have provided experimental evidence of such impairment. To provide additional information about the effects of these oligomers on memory, the present study examined the memory of groups of rats exposed to ICV injections of the culture media (CM) of Chinese Hamster Ovary cells that were (7PA2) and were not (CHO-) transfected with a human mutation of amyloid precursor protein that appears to cause early-onset Alzheimer's disease. The 7PA2 CM, which contained concentrations of soluble amyloid-β oligomers physiologically relevant to those found in human brain, significantly disrupted working memory in rats tested in a radial-arm maze. In contrast, CHO-CM, which did not contain such oligomers, had no effect on memory. The disruptive effects of 7PA2-derived amyloid-β oligomers, evident two hours after exposure, disappeared within a day. These findings are compared to results from 7PA2 CM tested under a complex procedure thought to measure aspects of executive function. The results confirm the disruptive effects of low-n amyloid-β oligomers and extend them to a well established rat model of memory.

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Clusterin

Nelsestuen

McDonald

2002

Wiley Encyclopedia of Molecular Medicine

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Clusterin (apoJ) Alters the Aggregation of Amyloid β-Peptide (Aβ1-42) and Forms Slowly Sedimenting Aβ Complexes That Cause Oxidative Stress

Cited by 342 publications

References 0 publications

Small Heat‐shock Proteins and Clusterin: Intra‐ and Extracellular Molecular Chaperones with a Common Mechanism of Action and Function?

Small Heat‐shock Proteins and Clusterin: Intra‐ and Extracellular Molecular Chaperones with a Common Mechanism of Action and Function?

Oligomers of the amyloid-β protein disrupt working memory: Confirmation with two behavioral procedures

Clusterin

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