June 2025: Research into basic protein structure has identified a new molecule that could lead to novel treatments for neurological disease, and open up applications in parasitology. Lipoamide specifically prevents cytoplasmic condensation of stress granule proteins. The new molecule – called lipoamide – can prevent the formation of liquid droplet structures inside cells that are linked with Motor Neurone Disease (MND).The findings were made by a large international team based at the Max Planck Institute of Molecular Cell Biology and Genetics, and led by Dr Richard Wheeler now at the School of Biological Sciences at the University of Edinburgh, while he was a postdoc with the team.They discovered lipoamide’s effects after screening 1,600 molecules to identify those affecting the formation of liquid droplets – known as stress granules – in cells. Busting stress granules Build-up of solid clumps of proteins inside stress granules – which normally only form briefly when cells are under stress – is one of the hallmarks of several neurodegenerative diseases, including MND.Lab tests in fly and worm disease models, and on motor neurons derived from MND patients, showed that lipoamide can dissolve existing stress granules and prevent new ones from forming. Further analysis found lipoamide also improved cell health, neuron structure and motor function. The findings are published in the journal Nature Chemical Biology. The research received support from the Wellcome Trust, Uehara Memorial Foundation, Japan Society for the Promotion of Science, and Japanese Biochemical Society. Read the paper in Nature Chemical Biology Importance of unstructured domains Unlike most drug molecules, lipoamide works by targeting floppy and unstructured parts of proteins – intrinsically disordered domains (IDRs) – that are needed to form stress granules, the team says.While it is encouraging to have a new way of targeting MND-associated proteins, it remains unclear exactly why lipoamide has beneficial effects, the team says. More research is needed to understand whether this is an effective new way to combat the build-up of stress granules leading to MND, they add. Identifying lipoamide powerfully demonstrates that drug-like molecules can target unstructured protein regions, with beneficial effects in experimental models of disease. Neurodegenerative diseases in people are often associated with unstructured proteins, making this an important demonstration of a potential new area for drug development. Dr Richard Wheeler School of Biological Sciences, University of Edinburgh Wider applicability of findings Although the work in this study focused on the potential applicability of lipoamide to tackle Motor Neurone Disease, the same principles may also open new opportunities to investigate druggable targets in IDR proteins for other diseases, including some infections.Study leader, Dr Richard Wheeler, said: The findings may also have implications for disease caused by unicellular parasites. These parasites often have a disproportionately large number of IDR-containing proteins. This study, demonstrating proof-of-concept for IDRs to act as druggable targets, could raise the possibility of novel therapeutics for these devastating diseases. More information Please contact: Corin Campbell, Press and PR Office, +44 (0)7920 404 319, corin.campbell@ed.ac.uk Related links Richard WheelerSchool of Biological SciencesInstitute of Immunology and Infection ResearchAntony HymanMax Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany This article was published on 2025-06-24
