AI Article Synopsis
- Parkinson's disease (PD) is a common neurodegenerative disorder, and early diagnosis is crucial yet challenging.
- Researchers have created new compounds called styrylaniline derivatives that can bind to alpha-synuclein (α-syn) aggregates, which are linked to PD.
- One particular compound, 7-16, not only effectively detects these aggregates in cells and mouse models but also can cross the blood-brain barrier, indicating its potential for use in imaging agents for PD diagnosis.
Article Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Early diagnosis is the key to treatment but is still a great challenge in the clinic now. The discovery of alpha-synuclein (α-syn) aggregates ligands has become an attractive strategy to meet the early diagnosis of PD. Herein, we designed and synthesized a series of styrylaniline derivatives as novel α-syn aggregates ligands. Several compounds displayed good potency to α-syn aggregates with K values less than 0.1 μM. The docking study revealed that the hydrogen bonds and cation-pi interaction between ligands and α-syn aggregates would be crucial for the activity. The representative compound 7-16 not only detected α-syn aggregates in both SH-SY5Y cells and brain tissues prepared from two kinds of α-syn preformed-fibrils-injected mice models but also showed good blood-brain barrier penetration characteristics in vivo with a brain/plasma ratio over 1.0, which demonstrates its potential as a lead compound for further development of in vivo imaging agents.
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| http://dx.doi.org/10.1016/j.ejmech.2021.113887 | DOI Listing |
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