Abstract
A genetic change that occurs in astrocyte cells in the brain and spinal cord causes them to become ‘reactive' and trigger the onset of the degenerative motor neuron disease amyotrophic lateral sclerosis (ALS), according to UK research.
“Understanding how astrocytes undergo this transformation is a really exciting step forward. It brings us closer to potentially being able to control and prevent astrocytes from becoming harmfully reactive,” says Rickie Patani, M.D., PhD., a professor at the Francis Crick Institute in London who led the research, which is published in the journal Nucleic Acids Research.
Astrocytes are known to be altered in people with conditions such as ALS, in neurological conditions like Parkinson's disease, or in those who have nervous system injuries.
In this study, Patani and colleagues compared astrocytes from ALS patients with healthy astrocytes. The cells from ALS patients had a lot of heavily spliced proteins where many non-coding introns had not been translated from the gene sequence, whereas in healthy astrocyte cells many intron regions are retained in the final proteins.
“Our group have previously shown that splicing is decreased in ALS motor neurons, so when we found the opposite in ALS astrocytes we were intrigued,” says Oliver Ziff, M.D., lead author on the paper and clinical fellow in Patani's group.
“Increased splicing is what we find in other immune cells when they become activated or angry. This raises the possibility that ALS astrocytes inflict a toxic immune insult on the nervous system and opens new therapeutic avenues for treating ALS.”
