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Updated: Jan 23, 2026

Technique for Intranasal Administration of α-Synuclein Aggregates
Published on: November 8, 2024
Anti-oligomerization sheet molecules: Design, synthesis and evaluation of inhibitory activities against α-synuclein
1College of Chemistry and Molecular Engineering, Zhengzhou University, Daxue Road 75, 450052 Zhengzhou, China.
Abstract:
Aggregation of α-synuclein (α-Syn) play a key role in the development of Parkinson Disease (PD). One of the effective approaches is to stabilize the native, monomeric protein with suitable molecule ligands. We have designed and synthesized a series of sheet-like conjugated compounds which possess different skeletons and various heteroatoms in the two blocks located at both ends of linker, which have good π-electron delocalization and high ability of hydrogen-bond formation. They have shown anti-aggregation activities in vitro towards α-Syn with IC50 down to 1.09 μM. The molecule is found binding in parallel to the NACore within NAC domain of α-Syn, interfering aggregation of NAC region within different α-Syn monomer, and further inhibiting or slowing down the formation of α-Syn oligomer nuclei at lag phase. The potential inhibitor obtained by our strategy is considered to be highly efficient to inhibit α-Syn aggregation.
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