New publication about the molecular mechanisms of protein aggregation


CEPLAS member Ernesto Llamas (UoC) reports together with David Vilchez (CECAD) about a potential therapy for Huntington's disease.

Ernesto Llamas
Confocal image of plant cells expressing a fragment of the human protein Huntingtin (green or orange depending which image you choose), one single cell is showing protein aggregation

Imagine if plants could help to find a cure for one of the most devastating neurodegenerative diseases in humans: Huntington’s disease. This is the question that motivated the research of a team of scientists from the CECAD and CEPLAS, who explored the possibility of using plants as a model system to study the molecular mechanisms of protein aggregation and toxicity.

Huntington’s disease is a genetic proteinopathy, a type of disease caused by the mutation of a specific gene that encodes for the protein huntingtin (HTT). This mutation leads to the production of an abnormal form of HTT that has an expanded polyglutamine (polyQ) tract, which makes it prone to form toxic protein aggregates in neurons. These aggregates interfere with the normal functioning of the cells and cause their death, resulting in progressive cognitive, motor and psychiatric symptoms.

To test if plants can develop similar symptoms to Huntington’s disease, the researchers first introduced the human HTT gene with the polyQ expansion into plants. They then observed that plants that have the human protein didn’t show toxic symptoms or cell death. But why? To answer this question, they performed a series of experiments that revealed that a chloroplast protein named Stromal Processing Peptidase (SPP for short) could be the reason why plants are resistant to the development of Huntington’s disease.

The results indicate that SPP prevents HTT from forming aggregates. To test this hypothesis, the researchers introduced the plant SPP gene into human cells and roundworms (C.elegans), which are commonly used as research models for Huntington’s disease. They saw a remarkable reduction of toxic protein aggregates in these models, as well as an improvement of their survival and behavior. These findings suggest that SPP could be a potential therapeutic target for treating Huntington’s disease and other diseases that involve toxic protein aggregates.

The research was published in the journal Nature Plants under the title “In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation”.

Text: Ernesto Llamas

More information