期刊
ACS CHEMICAL NEUROSCIENCE
卷 13, 期 5, 页码 581-586出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.1c00849
关键词
5-(4-pyridinyl)-1,2,4-triazoles; synthesis; Parkinson's disease; alpha synuclein; MPTP
资金
- Programma Operativo Nazionale Ricerca & Innovazione 2014-2020, Azione I.1 Dottorati Innovativi con caratterizzazione industriale [DOT1314952]
Parkinson's disease is characterized by the death of dopaminergic neurons and the formation of intracellular proteinaceous accumulations. A compound named 15 has been identified to effectively prevent Parkinson's disease symptoms and affect the levels of related markers. Furthermore, these compounds also slightly reduce protein aggregation.
Parkinson's disease (PD) is characterized by the death of dopaminergic neurons. The common histopathological hallmark in PD patients is the formation of intracellular proteinaceous accumulations. The main constituent of these inclusions is alpha-synuclein (alpha-syn), an intrinsically disordered protein that in pathological conditions creates amyloid aggregates that lead to neurotoxicity and neurodegeneration. The main goal of our study was to optimize our previously identified alpha-syn aggregation inhibitors of 5-(4-pyridinyl)-1,2,4-triazole chemotype in terms of in vivo efficacy. Our efforts resulted in the identification of ethyl 2-((4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetate (15), which displayed the ability to prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine-induced bradykinesia as well as to affect the levels of PD markers after the administration of the same neurotoxin. In addition to the in vivo evaluation, for the 5-(4-pyridinyl)-1,2,4-triazole-based compounds, we measured the prevention of the fibrillization process using light scattering and a ThT binding assay; these compounds have been shown to slightly reduce the alpha-syn aggregation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据