Beetroot peptide as potential drug candidate for treating neurodegenerative and inflammatory diseases
Peptide is able to inhibit a particular enzyme that is responsible for the breakdown of messenger molecules in the body
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The beetroot peptide specifically inhibits prolyl oligopeptidase (POP), which is involved in the breakdown of protein hormones in the body and is therefore able to regulate inflammatory reactions. POP is a much-discussed drug target for neurodegenerative and inflammatory diseases, such as Alzheimer's and multiple sclerosis, for example. "This means that, in future studies, this group of plant peptides called ‘knottins’, such as those found in beetroot, could potentially provide a drug candidate for treating these diseases."
Peptide can be detected in commercial beetroot juice
The peptide not only occurs in the root vegetables but can also be detected in commercially available beetroot juice – albeit in very low concentrations. "Although beetroot counts as a very healthy vegetable, it would be unreasonable to hope that dementia could be prevented by regular consumption of beetroot," stresses the MedUni Vienna pharmacologist. "The peptide only occurs in very small quantities and it is not clear whether it can as such be absorbed via the gastrointestinal tract."
Using Nature's blueprint
The research work being conducted by Gruber's laboratory utilized the idea of harnessing Nature's blueprint to develop drug candidates. "We are searching through large databases containing genetic information of plants and animals, decoding new types of peptide molecules and studying their structure, aiming to test them pharmacologically on enzymes or cellular receptors (such as one of the prominent drug target classes, the so-called G protein-coupled receptors) and finally analysing them in the disease models," explains Gruber. Potential drug candidates are chemically synthesised in a slightly modified form based on the natural product, in order to obtain optimised pharmacological properties. This concept appears to be successful: a few years ago the research team generated a drug candidate T20K for MS with a synthesised plant peptide (cyclotide), which has recently been tested successfully in a Phase 1 trial by the Swedish firm Cyxone under a MedUni Vienna licence, and is now being prepared for a Phase 2 clinical trial.
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Bernhard Retzl, Roland Hellinger, Edin Muratspahić, Meri E. F. Pinto, Vanderlan S. Bolzani, and Christian W. Gruber; "Discovery of a Beetroot Protease Inhibitor to Identify and Classify Plant-Derived Cystine Knot Peptides"; J. Nat. Prod.; 2020
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