Understanding the extension of DNA to the neurons of Huntington’s disease

The study reveals how the gradual expansion of the repetition of CAG to neurons leads the occurrence of Huntington’s disease, offering new ideas for possible therapeutic interventions.

Study: Long bodily DNA-Restoles Neurodegeneration in Huntington’s Disease. Credit Picture: Shutterstock ai / Shutterstock.com

A recent study published in Cell It reveals that the repeated DNA sequence leading to Huntington’s (HD) disease is slowly expanding to several decades to neuronal disease specialists, eventually leading to the production of these neurons and the onset of the disease.

What causes HD?

HD is a life -threatening neurodegenerative ill_n In Exono 1 of hunting (Htt) gene. This repetition CAG encodes a polygmine pathway within the HTT protein, which is involved in the regulation of gene expression, the transfer of materials between neurons and the protection of cells from death.

Compared to different healthy people with 15-30 consecutive Cags, people with HD usually have a 36-55-consecutive germalist allegory, with about 90% of these people inheriting 40-49 of these Cags.

For several decades, people with HD will not have symptoms. However, usually between 40 and 50 years, patients with HD will develop chorus, which describes uncontrolled movements that are characteristic of HD that often develop severe weakening, rigidity and mortality, along with cognitive and psychiatric symptoms.

Gradual neuronal degeneration driven by CAG extension

Despite existing evidence of the genetic base of HD, it remains unclear because the disease -causing mutation causes degeneration in specific neurons only during middle life after decades of biological latent period.

To explore this phenomenon, the researchers of the current study used ribonucleic acid sequence (RNA) (SNRNA-SEQ) to analyze RNA expression in 581,273 cores isolated from the front area of ​​the nucleus and area of ​​the brain most often affected in patients with HD. Samples of skyscrapers were obtained from patients with 50 HD and 53 unwanted checks with an average of 5,643 cores obtained from each donor.

The CAG-Age-Product (CAP) rating, which is often used to estimate the start and evolution of HD, was also used in resolution. To this end, HD patients with a CAP rating of up to 300 had slightly lower ratios of ribbing neurons (SPNS) compared to healthy witnesses, while people with CAP scores exceeding 350 showed a significant reduction in the abundance of SPN.

Specifically, a CAP rating of up to 300 is usually provided to patients with HD without clinical engine symptoms, while those with CAP ratings of 350 or more have HD symptoms. Patients with HD with CAP scores of 600 or more who often reflect patients with advanced Caudate atrophy lost 80-99% of their SPN .

In addition to the SPNS, the researchers also observed the differential expression of thousands of genes in each type of caudate cells between people with and without HD. This finding is an example of the deep caudate destruction that appears in HD.

CAG is repeated in Htt Gene was physically expanded from 40 to over 500 to SPNs. Physical expansion from 40 to 150 Cags did not significantly affect the health of neurons. However, the extension of 150 or more Cags resulted in the loss of positive and then negative characteristics of neuronal identity, deformed gene expression and ultimately the degeneration of the SPNs.

The computing extension of the experimental data was applied to determine the rate and time of expansion of CAG repetitions to SPN. To this end, there was a slow initial expansion that appeared less than once each year during the first two decades of life.

When a neuron earns 80 CAG repetitions, usually after several decades, the rate of expansion increases significantly and extends to 150 cags in a few more years. Months later, the neuron will die.

These findings indicate that SPN spends over 95% of their lives with a harmless Htt gene. Since different neurons reach the toxicity of CAG repetitions at different times, the neurons collectively and slowly disappear in a long time that usually begins about 20 years before the onset of symptoms and faster after the onset of symptoms.

Importance

The findings of the study provide important knowledge of HD pathophysiology and possibly other diseases that result from abnormal DNA repetition numbers, including Fragile x Syndrome and myotonic dystrophy. Encouraged by these findings, researchers in the current study are currently investigating how more than 150 CAG repetitions lead to neuronal damage and death, as well as the correlation between the expansion of repetitive DNA and cellular changes to other similar genetic disorders .

We were able to concentrate the complete pathology of the pathology as it unfolds in decades in individual neurons and this may give us many different times where we can intervene therapeutic. “