By James Gamble
A protein that allows plants to fight neurodegenerative diseases such as Huntington’s could be harnessed to help humans do the same, scientists say.
Researchers found a protein in plants that reduced the clumping of proteins responsible for the pathological changes in models of Huntington’s disease in humans.
The scientists from Cologne and Dusseldorf in Germany hope the model could soon be transferred to humans to help treat Huntington’s disease – which was believed to be incurable until now.
The study, published in the journal Nature Aging, followed an unconventional approach to finding potential drugs to treat polyglutamine (polyQ) diseases.
Huntington’s disease is among nine polyQ disorders – a group of neurodegenerative disorders caused by multiple repetitions of glutamine amino acids in specific proteins – known to affect humans.
Huntington’s is a rare, inherited condition that causes widespread deterioration in the brain and disrupts the sufferer’s thinking, behavior, emotion and movement.
In their latest study, the German researchers focused on plants – which are constantly challenged by the environment but cannot move to escape their conditions.
However, plants do possess a striking innate resilience to stress which increases their longevity.
Unlike humans, who suffer from “proteinopathies” caused by the toxic aggregation or cluster of proteins, plants do not experience these kinds of diseases.
They express hundreds of proteins containing polyQ repeats, but no explanations for these factors have yet been reported.
In order to explore how plants deal with toxic protein aggregation, Dr. Ernesto Llamas, the first author of the study, introduced the toxic mutant protein “huntingtin” into plants, which causes cell death in human neurons.
In contrast to animal and human models, they found that Arabidopsis thaliana plants – or thale cress – actively removed huntingtin protein clumps and avoided harmful effects.
Using synthetic biology, Dr. Llamas’ research team, from the University of Cologne’s CECAD Cluster of Excellence for Aging Research and the CEPLAS Cluster of Excellence for Plant Sciences, transferred the plants’ ability to avoid clustering into human-cultivated cells and animal models of Huntington’s disease.
The team’s hope is that the use of plant proteins could now lead to new therapeutic approaches for treating Huntington’s disease and other neurodegenerative diseases.
Professor Dr. David Vilchez of CECAD, explained: “We were surprised to see plants completely healthy, even though they were genetically producing the toxic human protein.
“The expression of mutant huntingtin in other models of research like human cultured cells, mice and nematode worms induce detrimental effects and symptoms of disease.”
The study team discovered that the plants avoided the toxic aggregation of mutant huntingtin due to their chloroplasts – plant-specific organelles that perform photosynthesis.
“Unlike humans,” Dr. Llamas said, “plants have chloroplasts: an extra cellular type of organelle that could provide an expanded molecular machinery to get rid of toxic protein aggregates.”
The multidisciplinary team identified the chloroplast plant protein SPP as the reason why plants are unaffected by the problematic human protein.
And they found that producing the plant SPP in models of Huntington’s disease such as human cultured cells and worms like the nematode C. elegans reduced protein clumps and symptoms of the disease.
“We were pleased to observe that expression of the plant SPP protein improved motility of C. elegans worms affected by huntingtin even at later aging stages where the symptoms are even worse,” said Dr. Hyun Ju Lee, a postdoc also involved in the study.
The results of Dr. Llamas’ team’s study could open the door for testing SPP as a potential therapy for Huntington’s disease.
He hopes plants could grow to play a bigger role in contributing to the treatment of human diseases.
“Many people don’t notice that plants can persist amongst variable and extreme environmental conditions that cause protein aggregation,” Dr. Llamas said.
“I believe that plant molecular mechanisms hold the key to discovering new drugs that can prevent human diseases.
“We usually forget that some plants can live thousands of years and should be studied as models of aging research.”
Dr. Seda Koyuncu, another postdoc involved in the study, added: “Over the past years, we have seen several promising approaches to treating hereditary diseases like Huntington’s fail.
“We are confident that our plant synthetic approach will lead to significant advances in the field.”
The team has since acquired funding from the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung; BMBF) through the GO-Bio initial program.
“We want to bring our idea into an application,” Dr. Llamas said.
“Our plan is to found a start-up to produce plant-derived therapeutic proteins and to test them as potential therapeutics to treat neurodegenerative diseases in humans.”
Produced in association with SWNS Talker