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Updated: Jan 24, 2026

Technique for Intranasal Administration of α-Synuclein Aggregates
Published on: November 8, 2024
Identification of a New α-Synuclein Aggregation Inhibitor via Mass Spectrometry Based Screening
Mingming Xu1, Wendy Loa-Kum-Cheung1, Haiyan Zhang2
1Griffith Institute for Drug Discovery , Griffith University , Don Young Road , Nathan , QLD 4111 , Australia.
Abstract:
The aggregation of disordered α-synuclein protein is pathogenically connected with Parkinson's disease. Therefore, discovering molecules that can inhibit the misfolding and aggregation of α-synuclein is an active research area in PD drug development. A key property of such required therapeutic agents is specific binding to the target protein. Mass spectrometry allows rapid detection of direct interactions between molecules and proteins and is an ideal technique for discovering specific α-synuclein binders. Here, by setting up an automated mass spectrometry-based screening system, we were able to screen over 2500 compounds and identify a new α-synuclein inhibitor, 3-[(3-methoxyphenyl)carbamoyl]-7-[( E)-2-phenylethenyl]-4,7-dihydropyrazolo [1,5- a]pyrimidine-5-carboxylic acid (compound 2). This compound not only significantly inhibits the misfolding and aggregation of α-synuclein and protects neuroblastoma cells from α-synuclein toxicity, but also has a more specific binding site compared with positive controls. Our work for the first time reports the inhibition of compound 2 on α-synuclein aggregation and also consolidates the capability of mass spectrometry to discover α-synuclein aggregation inhibitors.
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