Protein synthesis could be a potential therapeutic target for the treatment of Huntington’s disease. This is one of the conclusions of a new study, conducted in Spain, which shows how this mechanism participates in the degeneration of the neurons affected by the pathology.

Scientists from the Institute of Neurosciences at the University of Barcelona (UBNeuro) and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) described how the increase in protein synthesis is involved in the degeneration of the type of neurons affected in Huntington’s disease, a neurodegenerative genetic pathology.

These results, published in the scientific journal Brain, could serve to design new therapies to treat this and other diseases that affect the brain. The work is led by Esther Pérez Navarro, professor at the UB and IDIBAPS researcher. In addition, scientists from the Pablo de Olavide University also participated in the study.

Huntington’s disease is a genetic neurodegenerative disorder caused by the mutation of the huntington gene, which causes early loss of striatal projection neurons, with effects on motor coordination and cognitive and psychiatric impairment.

The new work analyzed the role of the alteration of protein synthesis in this process, a mechanism that allows neurons to read the genetic code to synthesize proteins. To study this mechanism, total and phosphorylated levels of 4E-BP1, a protein that inhibits protein synthesis, were analyzed in a mouse model of the disease.

The results show that the total levels of this protein are reduced, while phosphorylation levels increase, in the striatal projection neurons of mice with the ailment compared to control mice. So that protein synthesis increases, which we also found in samples of patients’ brains,” explains Pérez Navarro, also a researcher at the Biomedical Research Center in Network for Neurodegenerative Diseases (CIBERNED).

To confirm this relationship between the inappropriate activity of protein synthesis and the disease, the researchers pharmacologically blocked this mechanism and found that it improved the motor function of mice and that normal levels of different molecular values ​​in the brain were restored.

These results indicate that an increase in protein synthesis in Huntington’s disease is harmful and, therefore, is a potential therapeutic target for new treatments, such as a drug that can be supplied non-invasively to normalize protein synthesis,” details the researcher.

Common mechanism to other diseases of the brain

Although it is the first time that the alteration of protein synthesis is related to Huntington’s disease, it is a mechanism that has been described in other neurodegenerative diseases (such as Alzheimer’s and Parkinson’s ) and in other mental disorders, such as autism.

The fact of finding common mechanisms to different pathologies that affect our brain makes the finding more attractive, since the same therapy could be beneficial for several diseases,” says the researcher.

This research also opens the door to the identification of biomarkers to detect the disease before the first symptoms appear. In this sense, the researchers, in collaboration with the Parkinson’s and Movement Disorders Unit of the Santa Creu and Sant Pau Hospital, are studying whether protein synthesis is also altered in cells outside the brain, such as blood and fibroblasts (skin cells).

The advantage of carrying out this study with a disease such as Huntington’s disease, which is associated with a genetic mutation, is that we can analyze these changes in carrier individuals who still do not have symptoms and follow up over time,” concludes the researcher

 

Source: SINC