Could Plants Hold the Key to Neurodegenerative Diseases?

 by Hannah Watts

In humans, the aggregation of polyglutamine repeat (polyQ) proteins causes disorders such as Huntington’s disease. To date, nine polyQ disorders have been described in humans, all of which remain incurable with current treatment options provided by the NHS, focusing on quality of life rather than its preservation. An excessive number of polyQ repeats can cause proteins to aggregate or accumulate in harmful protein deposits, leading to cellular dysfunction and death. In the case of Huntington's disease, polyQ repeats cause widespread deterioration in brain structure, disrupting thinking, behaviour, emotion, and movement. However, new research suggests that plant chloroplasts could hold the answer.

Although plants express hundreds of polyQ-containing proteins, no pathologies arising from polyQ aggregation have been reported. In a recent study by researchers at the University of Cologne's CECAD Cluster of Excellence for Aging Research and the CEPLAS Cluster of Excellence for Plant Sciences, a promising synthetic plant biology approach for the development of therapy to treat human neurodegenerative diseases, especially Huntington's disease, was found. In the publication "In-planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation" in Nature Aging, they showed that a synthetic enzyme derived from plants - stromal processing peptidase (SPP) - reduces the clumping of proteins responsible for the pathological changes in models of Huntington's disease in human cells and the nematode Caenorhabditis elegans.

Plants possess a striking resilience to stress that allows them to live long, unlike humans who suffer from proteinopathies caused by the toxic aggregation or clustering of proteins, and aren’t found to carry these diseases. Despite expressing hundreds of proteins containing polyQ repeats, no pathologies from these factors have been reported. To explore how this works, Dr. Ernesto Llamas, first author of the study, and colleagues introduced the toxic mutant protein huntingtin in plants, which causes cell death in human neurons. In contrast to animal and human models, they found that Arabidopsis thaliana plants actively removed huntingtin protein clumps and avoided harmful effects. Through synthetic biology, the scientists then transferred this ability to avoid aggregation into human cultivated cells and animal models of Huntington's disease, finding that similar removal occurred.

Although this is not near a clinical trial, their hope is that the use of plant proteins could lead to new therapeutic approaches for treating Huntington's disease and other neurodegenerative diseases, as well as encouraging others to look to plants for new and innovative solutions.

References 

1. https://www.sciencedaily.com/releases/2023/10/231002124226.htm#:~:text=Summary%3A,for%20application%20in%20human%20cells.

2. https://www.nature.com/articles/s43587-023-00502-1#Abs1