期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 64, 期 11, 页码 7422-7433出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.1c00033
关键词
-
资金
- Tata Education and Development Trust
- Department of Biotechnology at the Indian Institute of Science, Bangalore
- NCBS (TIFR)
- JC Bose fellowship [SB/S2/JC-071/2015]
- DST-SERB (Early Career Award, Ramanujan Fellowship)
- Max Planck Society (Partner group program)
- Department of Biotechnology
The study reveals that cyclotides from Clitoria ternatea have neuroprotective effects against Aβ-induced toxicity in transgenic Caenorhabditis elegans, delaying paralysis and improving chemotaxis defects. The protection is likely mediated by inhibiting Aβ oligomerization and reducing Aβ deposits, indicating cyclotides as a potential pharmacophore scaffold for neurodegenerative diseases.
Neurotoxic aggregation of beta-amyloid (A beta) peptides is a hallmark of Alzheimer's disease and increased reactive oxygen species (ROS) is an associated process. In the present study, we report the neuroprotective effects of disulfide-rich, circular peptides from Clitoria ternatea (C. ternatea) (butterfly pea) on A beta-induced toxicity in transgenic Caenorhabditis elegans. Cyclotides (similar to 30 amino acids long) are a special class of cyclic cysteine knot peptides. We show that cyclotide-rich fractions from different plant tissues delay A beta-induced paralysis in the transgenic CL4176 strain expressing the human muscle-specific A beta(1-42) gene. They also improved A beta-induced chemotaxis defects in CL2355 strain expressing A beta(1-42) in the neuronal cells. ROS assay suggests that this protection is likely mediated by the inhibition of A beta oligomerization. Furthermore, A beta deposits were reduced in the CL2006 strain treated with the fractions. The study shows that cyclotides from C. ternatea could be a source of a novel pharmacophore scaffold against neurodegenerative diseases.
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