Kalmankar Neha V, Hari Hrudya, Sowdhamini Ramanathan, Venkatesan Radhika
National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore, Karnataka 560065, India.
The University of Trans-Disciplinary Health Sciences and Technology (TDU), #74/2, Jarakabande Kaval, Post Attur, via Yelahanka, Bangalore, Karnataka 560064, India.
J Med Chem. 2021 Jun 10;64(11):7422-7433. doi: 10.1021/acs.jmedchem.1c00033. Epub 2021 May 28.
Neurotoxic aggregation of β-amyloid (Aβ) 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 () (butterfly pea) on Aβ-induced toxicity in transgenic . Cyclotides (∼30 amino acids long) are a special class of cyclic cysteine knot peptides. We show that cyclotide-rich fractions from different plant tissues delay Aβ-induced paralysis in the transgenic CL4176 strain expressing the human muscle-specific Aβ gene. They also improved Aβ-induced chemotaxis defects in CL2355 strain expressing Aβ in the neuronal cells. ROS assay suggests that this protection is likely mediated by the inhibition of Aβ oligomerization. Furthermore, Aβ deposits were reduced in the CL2006 strain treated with the fractions. The study shows that cyclotides from could be a source of a novel pharmacophore scaffold against neurodegenerative diseases.
β-淀粉样蛋白(Aβ)肽的神经毒性聚集是阿尔茨海默病的一个标志,而活性氧(ROS)增加是一个相关过程。在本研究中,我们报告了来自蝶豆的富含二硫键的环肽对转基因秀丽隐杆线虫中Aβ诱导的毒性的神经保护作用。环肽(约30个氨基酸长)是一类特殊的环状半胱氨酸结肽。我们发现,来自不同植物组织的富含环肽的组分可延缓表达人类肌肉特异性Aβ基因的转基因CL4176品系中Aβ诱导的麻痹。它们还改善了在神经元细胞中表达Aβ的CL2355品系中Aβ诱导的趋化缺陷。ROS检测表明,这种保护作用可能是通过抑制Aβ寡聚化介导的。此外,用这些组分处理的CL2006品系中Aβ沉积物减少。该研究表明,来自蝶豆的环肽可能是一种新型药效团支架的来源,可用于对抗神经退行性疾病。