期刊
PHARMACEUTICALS
卷 14, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/ph14121330
关键词
Alzheimer's disease; polypharmacology; C; elegans; autophagy; drug discovery; zebrafish; 5XFAD mice
资金
- Tuscany Region (project: DEM-AGING)
- Telethon Grant Projects [GGP20011]
- Grant Dipartimenti di eccellenza 2018-2022, MIUR, Italyquot
In order to treat Alzheimer's disease, researchers designed a compound called SG2 with pleiotropic effects such as promoting autophagic flux, neuroprotection, and metabolic reprogramming. In animal model experiments, SG2 showed the ability to promote recovery in the AD model and improve learning abilities. This compound has been confirmed to have low toxicity, serving as a potential starting point for the development of AD drugs.
The identification of effective pharmacological tools for Alzheimer's disease (AD) represents one of the main challenges for therapeutic discovery. Due to the variety of pathological processes associated with AD, a promising route for pharmacological intervention involves the development of new chemical entities that can restore cellular homeostasis. To investigate this strategy, we designed and synthetized SG2, a compound related to the thyroid hormone thyroxine, that shares a pleiotropic activity with its endogenous parent compound, including autophagic flux promotion, neuroprotection, and metabolic reprogramming. We demonstrate herein that SG2 acts in a pleiotropic manner to induce recovery in a C. elegans model of AD based on the overexpression of A beta 42 and improves learning abilities in the 5XFAD mouse model of AD. Further, in vitro ADME-Tox profiling and toxicological studies in zebrafish confirmed the low toxicity of this compound, which represents a chemical starting point for AD drug development.
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