| First Author | Jang JY | Year | 2018 |
| Journal | Biochim Biophys Acta Gen Subj | Volume | 1862 |
| Issue | 1 | Pages | 71-80 |
| PubMed ID | 29107146 | Mgi Jnum | J:274302 |
| Mgi Id | MGI:6116093 | Doi | 10.1016/j.bbagen.2017.10.014 |
| Citation | Jang JY, et al. (2018) NABi, a novel beta-sheet breaker, inhibits Abeta aggregation and neuronal toxicity: Therapeutic implications for Alzheimer's disease. Biochim Biophys Acta 1862(1):71-80 |
| abstractText | Amyloid beta (Abeta) 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 Abeta aggregates have the cross-beta-structure, a common structural feature in amyloids, we systemically designed the Abeta-aggregation inhibitor that maintains Abeta-interacting ability but removes toxic part from SOD1 (superoxide dismutase 1)-G93A. We identified NABi (Natural Abeta Binder and Abeta-aggregation inhibitor) composed of beta2-3 strands, a novel breaker of Abeta aggregation, which does not self-aggregate and has no cytotoxicity at all. The NABi blocks Abeta-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 beta-sheet proteins other than Abeta. |
