Chloroplasts Show Promise as a Gene Therapy Tool for Huntington’s Disease: Study

Huntington's disease is a devastating neurodegenerative disorder that affects millions of people worldwide.

It is caused by a mutation in the gene encoding the protein huntingtin, which leads to the formation of toxic aggregates or clumps of the protein in the brain.

These aggregates interference with the normal functioning of neurons and cause progressive cognitive, behavioral, and motor symptoms.

There is currently no cure for Huntington's disease, and existing treatments only provide symptomatic relief.

However, a recent study by researchers at the University of Cologne in Germany has revealed a promising new approach for developing a therapy to treat Huntington's disease and other similar disorders.

The researchers discovered that plants have a remarkable ability to prevent protein aggregation and protect themselves from stress.

They found that a synthetic enzyme derived from plant chloroplasts can reduce the clumping of huntingtin protein and improve the survival of cells and animals affected by Huntington's disease.

How plants avoid protein aggregation

(Photo : ROBYN BECK/AFP via Getty Images)

Plants are constantly exposed to environmental challenges, such as drought, heat, cold and pathogens.

Unlike animals, they cannot move away from these stressful conditions, so they have evolved sophisticated mechanisms to cope with them.

One of these mechanisms involves the use of chloroplasts, the organelles that perform photosynthesis and produce energy for the plant.

Chloroplasts are also involved in the synthesis and processing of many proteins that are essential for plant growth and development.

Some of these proteins contain long stretches of glutamine amino acids, known as polyglutamine (polyQ) repeats.

In humans, an excessive number of polyQ repeats in certain proteins can cause them to aggregate and trigger neurodegenerative diseases, such as Huntington's disease, spinocerebellar ataxia, and dentatorubral-pallidoluysian atrophy.

However, plants do not suffer from these diseases, despite expressing hundreds of proteins with polyQ repeats.

The researchers wondered how plants avoid the harmful effects of polyQ proteins.

To investigate this question, they introduced the mutant huntingtin protein, which causes Huntington's disease in humans, into Arabidopsis thaliana plants.

They expected that the plants would show signs of toxicity and damage from the protein aggregation, but they were surprised to find that the plants were completely healthy and showed no signs of stress.

The researchers then identified the molecular mechanism that allows plants to prevent protein aggregation.

They found that a chloroplast enzyme called stromal processing peptidase (SPP) plays a key role in this process.

SPP is responsible for removing a signal peptide from newly synthesized proteins that are destined for the chloroplast.

However, SPP can also recognize and cleave polyQ proteins, such as huntingtin, and prevent them from forming aggregates.

Also Read: Paternal Plants Could Also Share Its Chloroplasts to Its Offspring [STUDY]

How SPP can help treat Huntington's disease

The researchers then tested whether SPP could also reduce protein aggregation and improve survival in human cells and animal models of Huntington's disease.

They used synthetic biology techniques to transfer SPP from plants into human cultured cells and nematodes (Caenorhabditis elegans) that express the mutant huntingtin protein.

They found that SPP significantly reduced the amount of huntingtin aggregates and increased the viability of both cell types.

The researchers also observed that SPP improved the behavioral and motor performance of the nematodes affected by Huntington's disease.

For example, SPP increased their ability to move normally and avoid harmful stimuli. These results suggest that SPP can protect neurons from the toxic effects of huntingtin aggregation and improve their function.

The researchers hoped that their findings will pave the way for developing new therapeutic strategies for treating Huntington's disease and other polyQ diseases.

They proposed that SPP could be delivered into human cells using gene therapy or nanoparticles, or that small molecules that mimic SPP activity could be developed as drugs.

They also plan to test whether SPP can prevent or delay the onset of symptoms in mouse models of Huntington's disease.

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