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Biochim Biophys Acta Gen Subj. 2018 Jan;1862(1):71-80. doi: 10.1016/j.bbagen.2017.10.014. Epub 2017 Oct 26.

NABi, a novel β-sheet breaker, inhibits Aβ aggregation and neuronal toxicity: Therapeutic implications for Alzheimer's disease.

Author information

1
Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
2
Department of Medical Life Sciences, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea. Electronic address: hrhim@catholic.ac.kr.
3
Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea. Electronic address: skang@korea.ac.kr.

Abstract

Amyloid beta (Aβ) aggregates are an important therapeutic target for Alzheimer's disease (AD), a fatal neurodegenerative disease. To date, AD still remains a big challenge due to no effective treatments. Based on the property that Aβ aggregates have the cross-β-structure, a common structural feature in amyloids, we systemically designed the Aβ-aggregation inhibitor that maintains Aβ-interacting ability but removes toxic part from SOD1 (superoxide dismutase 1)-G93A. We identified NABi (Natural Aβ Binder and Aβ-aggregation inhibitor) composed of β2-3 strands, a novel breaker of Aβ aggregation, which does not self-aggregate and has no cytotoxicity at all. The NABi blocks Aβ-fibril formation in vitro and in vivo and prevents neuronal cell death, a hallmark of AD pathogenesis. Such anti-amyloidogenic properties can provide novel strategies for treating AD. Furthermore, our study provides molecular insights into the design of amyloidogenic inhibitors to cure various neurodegenerative and amyloid-associated diseases, as NABi would regulate aggregation of other toxic β-sheet proteins other than Aβ.

PMID:
29107146
DOI:
10.1016/j.bbagen.2017.10.014
[Indexed for MEDLINE]

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