Mutations in noncoding DNA protect the brain from Amyotrophic Lateral Sclerosis (ALS)

Weizmann Institute of Science researchers discover a new neuroprotective pathway. 'We have identified mutations in this gene that reduce inflammation.'

By Israel National News

31.03.22

Genetic mutations linked to disease often spell bad news. Mutations in over 25 genes, for example, are associated with amyotrophic lateral sclerosis, or ALS, and they all increase the risk of developing this incurable disorder.

Now, a research team headed by Prof. Eran Hornstein of the Weizmann Institute of Science has linked a new gene to ALS, but this one contains mutations of a different sort: They seem to play a defensive, rather than an offensive, role in the disease.

The gene newly linked to ALS is located in the part of our genome once called “junk DNA.” This DNA makes up over 97 percent of the genome, but because it does not encode proteins, it used to be considered, well, junk.

Today, though this noncoding DNA is still regarded as biological dark matter, it’s already known to serve as a crucial instruction manual. Among other things, it determines when genes within the coding DNA – the ones that do encode proteins – are turned on and off.

Hornstein’s lab in Weizmann’s Molecular Neuroscience and Molecular Genetics Departments studies neurodegenerative diseases – that is, diseases in which neurons degenerate and die. The team is focusing on our noncoding DNA.

“This massive, noncoding part of the genome has been overlooked in the search for the genetic origins of neurodegenerative diseases like ALS,” Hornstein explains. “This is despite the fact that for most ALS cases, proteins cannot explain the emergence of the disease.”

Many people know about ALS thanks to the Ice Bucket Challenge that went viral a few years ago.

This rare neurological disease attacks motor neurons, the nerve cells responsible for controlling voluntary muscle movement involved in everything from walking to talking and breathing. The neurons gradually die off, ultimately causing respiratory failure and death.

One of the symptoms of ALS is inflammation in the brain regions connected to the dying neurons, caused by immune mechanisms in the brain.

“Our brain has an immune system,” explains Dr. Chen Eitan, who led the study in Hornstein’s lab together with Aviad Siany. “If you have a degenerative disease, your brain’s immune cells, called microglia, will try to protect you, attacking the cause of the neurodegeneration.”

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