Deep learning identifies TP-41 for methylglyoxal scavenging in Alzheimer's treatment
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초록

Rationale: Increased levels of advanced glycation end products (AGEs) have been observed in the brain tissues of patients with Alzheimer's disease (AD). Methylglyoxal (MGO) is a potent precursor of AGEs. To date, there have been no reports of utilizing deep learning (DL) technologies to target MGO scavengers for the development of AD therapeutics. Therefore, DL-driven approaches may play a crucial role in identifying potential MGO scavengers and candidates for Alzheimer's treatment. Methods: We developed "DeepMGO," a novel DL-based MGO scavenging activity prediction model, trained on 2,262 MGO scavenging activity assays from 660 compounds. Using this approach, we identified and validated TP-41 as a potential MGO scavenger in a mouse model of memory impairment. Results: DeepMGO demonstrated robust predictive performance and identified novel compounds with high MGO scavenging activity. TP-41 ameliorated depression symptoms and memory deficits in mouse models. Conclusions: Using DeepMGO, we identified TP-41 as a potential therapeutic agent for AD.

키워드

methylglyoxalAlzheimer's diseasedeep learningmemory impairmentdrug discoveryGLYCATION END-PRODUCTSOXIDATIVE STRESSALDOSE REDUCTASEENZYME-ACTIVITYIN-VITRODISEASECONSTITUENTSCOMPONENTSINHIBITORRECEPTOR
제목
Deep learning identifies TP-41 for methylglyoxal scavenging in Alzheimer's treatment
저자
Park, AronHong, Seong-MinLee, YeeunLee, JungeunJeon, SeunggyuSeo, Seung-YongLee, JinhyukKim, Seon-HyeokKo, Eun JiLee, Hae RanJung, Sang HeonBae, MunhyungKang, Min CheolPark, Myoung GyuNam, SeungyoonKim, Sun Yeou
DOI
10.7150/thno.111550
발행일
2026-01
유형
Article
저널명
Theranostics
16
3
페이지
1103 ~ 1122