They reveal the structure of the protein responsible for Huntington’s disease

2023-04-20 12:26:21

A team with the participation of researchers from the Institute of Advanced Chemistry of Catalonia (IQAC) of the Higher Council for Scientific Research (CSIC) has revealed the structure of the protein responsible for the Huntington’s diseasea pathology neurodegenerative severe disease characterized by progressive disorder of movement and cognitive function.

The results of the work, published in the journal Nature Structural and Molecular Biologypave the way towards a better understanding of the disease, as it provides new clues about the mechanism that triggers the formation of protein aggregates in it brain of these patients.

Huntington’s disease is triggered by a genetic mutation It affects the huntingtin protein. This defect is due to the expansion of the cytosine, adenine and guanine nucleotides, which are responsible for encoding in the DNA the synthesis of glutamine, one of the 20 amino acids involved in the composition of proteins. As a result, the number of glutamines in the protein increases, something that is directly related to the formation of protein aggregates in the brain.

In Spain it is estimated that more than 4,000 people suffer from Huntington’s disease

Although the function of the huntingtin protein is unknown, until now it is known that it is involved in neurological development and that a minimum number of glutamine amino acid molecules is necessary for this development. But there is a threshold of glutamine repeats in the huntingtin protein above which a person develops the disease. The healthy population has between 17 and 23 consecutive glutaminesbut above 36 they develop the symptoms of the illness.

The disease, considered rare, affects approximately one in 10,000 inhabitants in most European countries, although it also exists in the rest of the world in different proportions. In Spain, it is estimated that more than 4,000 people suffer from it, according to the Spanish Association of Huntington’s Korea.

a new perspective

“Although the basis of the disease is not yet established, it is believed that these additional glutamine repeats cause proteins to interact with each other and facilitate the formation of protein precipitates and clumps, resulting in the neural degeneration and in symptoms such as loss of coordination and dementia”, details Ramon CrehuetCSIC researcher at IQAC and one of the signatories of the work led by Pau Bernadófrom the Structural Biology Center of Montpellier (France).

The study provides a new perspective on the pathological threshold of the disease, which goes beyond the length of the glutamine repeat chain.

The Spanish scientist indicates that “it is known that the protein with a certain number of glutamines makes the appearance of the disease more prone, but we still do not fully understand why the structure of the protein changes and becomes more toxic.”

Now, the results of this research reveal that there is no qualitative change enter here structure of huntingtin with a pathological repeat number of glutamine, and huntingin of healthy people. There are only gradual changes that increase as the number of glutamines increases.

Our results provide a new perspective on the pathological threshold disease that goes beyond the length of the glutamine repeat chain. Knowing the structure of the protein and the mechanism of its aggregation may be the first step in designing drugs that help alleviate symptoms and improve the lives of patients”, highlights the CSIC researcher.

Exploring the structure of proteins can open up new possibilities for a better understanding of three nucleotide expansion diseases, among which, in addition to Huntington’s disease, are Kennedy’s disease, myotonic dystrophy or Syndrome of the brittle x.

Rights: Creative Commons.