Researchers tested ultra-stable cyclic peptides, of ~30 residue length that extracted from the plant on the worms and recorded the impact on the neurons.
One way of tackling the progression of Alzheimer’s disease (AD) is to prevent the underlying adverse changes in the brain. A team of researchers from the National Centre for Biological Sciences (NCBS) has recently published a study in the Journal of Medicinal Chemistry, dedicated to neuroprotection against these toxic changes. They used Caenorhabditis elegans and the butterfly pea plant for their exploration. Clitoria ternatea, or the butterfly pea plant has long been used in traditional medicine in India. As the lead author of the study, Neha V. Kalmankar says, “Plants have hundreds of compounds that could be repurposed for the benefit of society but the first step is to find which ones have the potential for medicinal purposes.” Based on existing academic knowledge of its therapeutic properties, the research team extracted and isolated a set of ultra-stable cyclic peptides (or “cyclotides”) from the plant. They tested these peptides of ~30 residue length on the worms and recorded the impact on the neurons.
Neurons in the human brain synthesize a protein called amyloid beta (Aβ). In patients with Alzheimer’s, these proteins undergo a process called aggregation, where they form large deposits (plaques). The aggregates are toxic to the cells and impair the important tasks neurons need to carry out. This neurotoxicity can be duplicated in the transgenic worms too—manifesting as paralysis in the muscles, chemotaxis defects such as movement deficits towards chemical cues, and oxidative stress. The experiments showed that the cyclotides from the plant protected the neurons against the amyloid aggregate formation. The worms which fed on the cyclotides showed significantly less paralysis than the ones that did not. They also showed that these peptide mixtures displayed antioxidant properties, an already well-established role of the plant. The different experiments provide strong evidence for the beneficial value of cyclotides, given that oxidative stress is a commonly related process in AD progression. Other age-related neurodegenerative disorders such as Parkinson’s disease and Huntington’s disease are also associated with the accumulation of toxic proteins, and this research avenue could lead to treatment options for several such diseases. Dr. Radhika Venkatesan, the corresponding author, explains, “Using a soil-dwelling nematode like C. elegans as a model is extremely valuable as these worms have conserved gene function, short life cycle and are experimentally tractable. They are excellent models to screen for therapeutic leads”.
Source: National Centre for Biological Sciences news release
