Cytotoxic Aβ Protofilaments Are Generated in the Process of Aβ Fibril Disaggregation
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei, Tokyo 184-8588, Japan
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Authors to whom correspondence should be addressed.
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These authors contributed equally to this work.
Academic Editor: Patrizia Hrelia
Int. J. Mol. Sci. 2021, 22(23), 12780; https://doi.org/10.3390/ijms222312780
Received: 29 October 2021
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Revised: 22 November 2021
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Accepted: 22 November 2021
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Published: 26 November 2021
(This article belongs to the Special Issue Amyloid Toxicity in Alzheimer's Disease)
Significant research on Alzheimer’s disease (AD) has demonstrated that amyloid β (Aβ) oligomers are toxic molecules against neural cells. Thus, determining the generation mechanism of toxic Aβ oligomers is crucial for understanding AD pathogenesis. Aβ fibrils were reported to be disaggregated by treatment with small compounds, such as epigallocatechin gallate (EGCG) and dopamine (DA), and a loss of fibril shape and decrease in cytotoxicity were observed. However, the characteristics of intermediate products during the fibril disaggregation process are poorly understood. In this study, we found that cytotoxic Aβ aggregates are generated during a moderate disaggregation process of Aβ fibrils. A cytotoxicity assay revealed that Aβ fibrils incubated with a low concentration of EGCG and DA showed higher cytotoxicity than Aβ fibrils alone. Atomic force microscopy imaging and circular dichroism spectrometry showed that short and narrow protofilaments, which were highly stable in the β-sheet structure, were abundant in these moderately disaggregated samples. These results indicate that toxic Aβ protofilaments are generated during disaggregation from amyloid fibrils, suggesting that disaggregation of Aβ fibrils by small compounds may be one of the possible mechanisms for the generation of toxic Aβ aggregates in the brain.
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Keywords:
Alzheimer’s disease; disaggregation; amyloid β; protofilaments; EGCG; dopamine
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MDPI and ACS Style
Kaku, T.; Tsukakoshi, K.; Ikebukuro, K. Cytotoxic Aβ Protofilaments Are Generated in the Process of Aβ Fibril Disaggregation. Int. J. Mol. Sci. 2021, 22, 12780. https://doi.org/10.3390/ijms222312780
AMA Style
Kaku T, Tsukakoshi K, Ikebukuro K. Cytotoxic Aβ Protofilaments Are Generated in the Process of Aβ Fibril Disaggregation. International Journal of Molecular Sciences. 2021; 22(23):12780. https://doi.org/10.3390/ijms222312780
Chicago/Turabian StyleKaku, Toshisuke, Kaori Tsukakoshi, and Kazunori Ikebukuro. 2021. "Cytotoxic Aβ Protofilaments Are Generated in the Process of Aβ Fibril Disaggregation" International Journal of Molecular Sciences 22, no. 23: 12780. https://doi.org/10.3390/ijms222312780
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