[Seminar 2] Anti-Alzheimer Strategies Utilizing Pathogenic Aβ Dimers By Prof. Young-Soo Kim

Title: Anti-Alzheimer Strategies Utilizing Pathogenic Aβ Dimers

Speaker: Prof. Young-Soo Kim
                Department of Pharmacy, Yonsei University, South Korea

Abstract:
Soluble amyloid-β (Aβ) oligomers, particularly toxic dimers, are increasingly recognized as key mediators of neurodegeneration in Alzheimer’s disease (AD). However, their structural heterogeneity has posed significant challenges for drug development. In this study, we introduce two complementary therapeutic strategies that converge on a defined pathogenic t, Aβ dimers. First, we established a synthetic platform using well-defined parallel and anti-parallel Aβ dimers and identified two FDA-approved compounds that effectively dissociate Aβ oligomers and plaques into monomers in 5XFAD transgenic mice, thereby reducing amyloid burden and restoring cognitive function. Second, we developed DAB0117, a blood–brain barrier-permeable dimeric peptidomimetic derived from the N-terminal fragment of Aβ. DAB selectively interacts with aggregated Aβ species, facilitating their disassembly. In vivo studies in 5XFAD mice demonstrated that DAB reduced amyloid deposition, attenuated neuroinflammation, and rescued memory deficits.

References
(1) Angewandte Chemie International Edition. 2023, 62(7), e202210209. Amyloid against amyloid: dimeric amyloid fragment ameliorates cognitive impairments by direct clearance of oligomers and plaques.
(2) Angewandte Chemie International Edition. 2020, 59(28), 11491. Discovery of chemicals to either clear or indicate amyloid aggregates by targeting memory‐impairing anti‐parallel Aβ dimers.

Host: Prod. Fujie Tanaka (Tanaka Unit)