A protein called Staufen1 accumulates in the cells of patients with ataxia or amyotrophic lateral sclerosis (ALS). Depleting this protein from affected mice helped improve symptoms, including motor function, researchers suggest.

Targeting Staufen1 could have therapeutic potential in people, suggest a study from University of Utah researchers and published in Nature Communications.

Previously, researchers had not considered Staufen1 a culprit in neurodegenerative disease until they discovered its association with ataxia. They found that Staufen1 binds Ataxin2, a protein that is both responsible for ataxia and a risk factor for ALS.

A role for Staufen1 in disease pathology became evident upon genetically depleting it from mice with an ataxia-like condition. The animals’ condition improved at both physiological and molecular levels, explains a media release from University of Utah Health.

Beginning at 12 weeks of age, mice performed significantly better on a rotarod performance test, measuring the length of time the animals could walk or run on an accelerating spinning rod. In addition, the expression of a handful of proteins that had diminished in brain cells during disease reverted back to near-normal levels.

“Staufen was first discovered in the fruit fly and has been studied for 30 years, but it had never been connected to anything related to disease. This is a novel finding,” says Stefan Pulst, MD, Dr Med, chair of Neurology at U of U Health and the study’s senior researcher.

Future investigations will focus on determining whether drugs or therapies that reduce Staufen1 could be developed as treatments for multiple diseases.

Beyond these applications, the biology of Staufen1 could reveal new clues about neurodegenerative disease. The protein accumulates with Ataxin2 and other proteins and RNAs in dense clusters called stress granules, a hallmark of ataxia, ALS and other conditions such as frontotemporal dementia. When Staufen1 was depleted from mice with ataxia, it not only improved the pathology of disease but also rid cells of stress granules, the release continues.

While the precise role of stress granules is still an intensive area of study, they are believed to help cells weather stress caused by toxins or certain disease conditions, explains co-author Daniel Scoles, PhD, associate professor of Neurology at U of U Health. One function could be to prevent proteins from being made under suboptimal conditions.

The findings connect Staufen1 to the emerging concept that neurodegenerative diseases are linked to malfunctions in the way cells cope with cellular stress. One implication, Scoles, adds, is that Staufen1-targeted therapies could work against a number of disorders in which stress granules emerge, although it remains to be determined whether the aggregates themselves lead to disease.

“Our results put the stress granule in focus as a structure to target in disease,” he says.

[Source(s): University of Utah Health, EurekAlert]