Scientists at the Francis Crick Institute and UCL have identified a major cell change in amyotrophic lateral sclerosis (ALS), a type of disease of motor neurons. The findings could help develop new treatments for many neurological diseases with the same modification, including Parkinson’s Disease and Alzheimer’s.
When the nervous system is injured, evaporated or infected, star-shaped cells, called astrocytes, undergo ‘reactive’ changes in their behavior. While some of these reactive astrocytes become immune, others cause damage and damage to motor neurons.
Reactive astrocytes are monitored in a number of neurodegenerative diseases including ALS, but there is a lack of understanding of what causes astrocytes to undergo this change.
In their research, published in Nucleic Equipment Research today (March 4), the scientists compared ALS-infected astrocytes with healthy astrocytes to find out how the diseased cells become reactive. These cells were grown from human-induced pluripotent gas cells – major gas cells – that can be directed to differentiate into any cell in the human body.
They found that an increase in the removal of uterus (uncoded segments of genetic information) from RNA in a process called splicing, is fundamental to the astrocyte transformation in diseased cells. The team pointed out that healthy astrocytes contain some RNA that normally encloses some uterus but in diseased cells these specific enzymes are secreted out.
This has a major impact on cell functions because when these enzymes are excreted from RNA, the remaining exons (coded extracts of genetic information) are used as a recipe for proteins. and some of these proteins in the astrocytes are partially altered.
Understanding how astrocytes undergo this transformation is a very interesting step. It will bring us closer to being able to control and prevent astrocytes from producing a harmful reaction. Although there is still a long way to go, we hope that it is possible to develop such a treatment and that it could even be used across all brain conditions in which an increase in reactive astrocytes is also recorded, including Parkinson’s Disease and Alzheimer’s. “
Rickie Patani, Principal Research Author and Group Director, Francis Crick Institute, Professor, UCL Queen’s Square Neurology Institute
Patani is also a Consultant Neurologist at the National Hospital for Neurology and Neurosurgery.ALS is a degenerative disease that progresses rapidly. Patients usually suffer from loss of movement, speech and eventually the ability to breathe, and most people survive only 3 to 5 years after diagnosis. There are currently no treatments that can significantly change the prognosis.
However, understanding the key cell changes associated with ALS could help develop new therapies to reduce disease progression.
Oliver Ziff, lead author and clinician at The Crick, UCL ‘s Queen’s Square Neurology Institute and registrar of neurology at the National Hospital for Neurology and Neurosurgery, says: “Our organization has previously shown that splicing reduced in ALS motor neurons, so when we found the opposite in ALS astrocytes we were inoculated.In fact, it is more splicing that we find in other immune cells as we grow. active or angry. This raises the possibility that ALS astrocytes exert a toxic immune barrier on the nervous system and open new therapeutic pathways for the treatment of ALS. “
The researchers will continue this work to further understand the molecular mechanisms involved when astrocytes become reactive with the goal of developing a potential intervention by doctors. used to reduce the progression of disease.
Source:
Francis Crick Institute