Machado-Joseph: Portuguese discover that internal biological clock is deeply affected

Less robustness and stability of circadian rhythm, greater break in the patterns of recessed activity, less efficiency and less sleep time.

The disease of Machado-Joseph It is a rare and hereditary neurodegenerative condition that affects the coordination of movements, balance, speech, swallowing and other essential functions.

More frequent in the Azores, and also known as Type 3 Espinocerebele Ataxia, continues to have a cure. But there are advances, to get to know this problem better and better.

Now, one of researchers from the University of Coimbra (UC) found that the Internal biological clock is deeply affected in people with the disease of Machado-Joseph.

For the first time, it was shown that in this disease there are changes in circadian rhythms – natural biological cycles of approximately 24 hours, which regulate the functioning of the body, including sleep, body temperature and physical activity.

“What we found was that the Circadian rhythm is losing its robustness as the disease advances. We also realize that the altered protein in people with this disease-Ataxina-3-interferes with the signs that the brain sends to keep the body to function in a synchronized manner. It is as if the internal clock ceased to give the right hours, ”explains the study leader, Rodrigo Ribeiro.

The research team studied the circadian rhythms and characterized their disturbances, discovering reduced and more fragmented levels of activity, difficulty in synchronization to sudden variations in the light scheme, and dysfunction in the rhythms of internal body temperature.

These data reveal that those who live with this disease present Less regularity at sleep and vigilhas greater difficulty adapting to changes in the environment (such as jet lag) and records unusual changes in body temperature.

The study involved people with Machado-Joseph disease, using monitoring bracelets (actigraphs), which record moments of sleep and activity.

Through this monitoring, they were identified severe changes in the parameters of the circadian rhythm correlated with the clinical progression of the disease.

People with Machado-Joseph disease present, for example, MINOR ROBUSTE AND STABILITY of the circadian rhythm, Greater break in the standards of active activityas well as decreased efficiency and total sleep time.

At the same time, animal and cellular models were used to study how the disease affects brain function throughout the day.

The study also shows that protein Ataxina-3 It helps activate genes that regulate the circadian rhythm.

However, in its altered version-the mutated Ataxina-3, characteristic of Machado-Joseph’s disease-this capacity ceases to function properly.

And this helps to explain why circadian rhythms are disorganized as the disease advances.

“Understanding the dysfunction of the biological clock is crucial not only to deepen the knowledge of the pathophysiology of the disease, but also to establish bases for the identification of biomarkers to monitor their progression,” adds cocoordinator Luís Pereira de Almeida.