The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Spherical aggregates of β-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3β
Open accessAbstract
β-Amyloid (Aβ) acquires toxicity by self-aggregation. To identify and characterize the toxic form(s) of Aβ aggregates, we examined in vitro aggregation conditions by using large quantities of homogenous, chemically synthesized Aβ 1–40 peptide. We found that slow rotation of Aβ 1–40 solution reproducibly gave self-aggregated Aβ 1–40 containing a stable and highly toxic moiety. Examination of the aggregates purified by glycerol-gradient centrifugation by atomic force microscopy and transmission electron microscopy revealed that the toxic moiety is a perfect sphere, which we call amylospheroid (ASPD). Other Aβ 1–40 aggregates, including fibrils, were nontoxic. Correlation studies between toxicity and sphere size indicate that 10- to 15-nm ASPD was highly toxic, whereas ASPD <10 nm was nontoxic. A positive correlation between the toxicity and ASPD >10 nm also appeared to exist when Aβ 1–42 formed ASPD by slow rotation. However, Aβ 1–42 -ASPD formed more rapidly, killed neurons at lower concentrations, and showed ≈100-fold-higher toxicity than Aβ 1–40 -ASPD. The toxic ASPD was associated with SDS-resistant oligomeric bands in immunoblotting, which were absent in nontoxic ASPD. Because the formation of ASPD was not disturbed by pentapeptides that break β-sheet interactions, Aβ may form ASPD through a pathway that is at least partly distinct from that of fibril formation. Inhibition experiments with lithium suggest the involvement of tau protein kinase I/glycogen synthase kinase-3β in the early stages of ASPD-induced neurodegeneration. Here we describe the identification and characterization of ASPD and discuss its possible role in the neurodegeneration in Alzheimer's disease.
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Cites
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Cited by
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade
Chiti, F., & Dobson, C. M. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-045115 · Cited by 2,629
The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes
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Aβ Oligomers – a decade of discovery
Walsh, D. M., & Selkoe, D. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04426.x · Cited by 1,938
Gaggelli, E., Kozlowski, H., Valensin, D., & Valensin, G. (2006) · Chemical Reviews · doi:10.1021/cr040410w · Cited by 1,729
Metadata
- Authors
- Hoshi, M., Sato, M., Matsumoto, S., Noguchi, A., Yasutake, K., Yoshida, N., & Sato, K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-05-15
- Volume
- 100
- Issue
- 11
- Pages
- 6370-6375
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1972456354
- Cited by
- 496
- References
- 13
- FWCI
- 17.91
- Type
- journal article
- Language
- en
- Open access
- green
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- Hoshi, M., Sato, M., Matsumoto, S., Noguchi, A., Yasutake, K., Yoshida, N., & Sato, K. (2003). Spherical aggregates of β-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3β. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1237107100
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