Stress granules are linked to a range of neurodegenerative diseases. Understanding of proteins associated with neurodegenerative diseases which can pave the way to new treatment approaches for disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS).

‘Stress granules are associated with a range of neurodegenerative diseases. Understanding of proteins associated with neurodegenerative diseases which can pave the way to new treatment approaches for disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS).’

As stress granules are linked to a range of neurodegenerative diseases, understanding how they form, and how they can be reduced, is of great interest to the medical world.
The study reveals the important role of two enzymes in disassembling stress granules.
These two enzymes, named USP5 and USP13, belong to a group of nearly 100 known deubiquitylases, which are thought to work by cutting ubiquitin chains inside stress granules.




The study is the culmination of over five years of work by the team, including Masayuki Komada, Toshiaki Fukushima and Shunsuke Matsumoto of Tokyo Institute of Technology (Tokyo Tech). First author Xuan Xie, a Ph.D. student at the laboratory led by Komada, has described how they arrived at their 'eureka' moment in an interview with the journal's First Person series.
As a first step, the researchers demonstrated that USP5 and USP13 are preferentially recruited to heat-induced stress granules.
"We found that heat-induced stress granules contain ubiquitin chains, much more so than in stress granules induced by other stressors," explains Fukushima. "This implied that ubiquitin chains might recruit USP5 and USP13 to stress granules."
Importantly, as ubiquitin chains are often found in stress granules in neurodegenerative diseases, the heat-induced stress granules provided a good model for further investigation.
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The findings suggest that the presence of USP5 and USP13 is critical to the disassembly of stress granules.
"We concluded that both reactions are required for the efficient destabilization of stress granules," says Fukushima.
The study may lead to the development of "artificial deubiquitinating enzymes," which could have a profound impact on future medical treatments.
Developing such innovative enzymes that "possess high activity and show specific localization to stress granules" is a feat that could be achieved in five years, Fukushima adds.
Source-Eurekalert