Lou Gehrig`s disease`s mechanism identified
Washington: Researchers have linked the toxic build-up of certain proteins and related molecules in cells, including neurons, to mutations in a gene that causes amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders.
St. Jude Children`s Research Hospital scientists` new findings have provided the first evidence that a gene named VCP plays a role in the break-up and clearance of protein and RNA molecules that accumulate in temporary structures called RNA granules.
RNAs perform a variety of vital cell functions, including protein production. RNA granules support proper functioning of RNA.
In ALS and related degenerative diseases, the process of assembling and clearing RNA granules is impaired. The proteins and RNAs associated with the granules often build up in nerve cells of patients. This study shows how mutations in VCP might contribute to that process and neurodegenerative disease.
Roy Parker, Ph.D., of the University of Colorado`s Department of Chemistry and Biochemistry and the Howard Hughes Medical Institute (HHMI), said that a strength of this study is that it provides a unifying hypothesis about how different genetic mutations all affect stress granules, which suggests that understanding stress granule dynamics and how they can be manipulated might be beneficial for treatment of these diseases.
Regina-Maria Kolaitis, Ph.D., a postdoctoral fellow in Taylor`s laboratory said that the research also tiesVCP mutations to disruption of RNA regulation, which prior studies have connected to the progression of neurodegenerative diseases.
For this study, researchers used yeast to identify a network of 125 genes that affect the formation and behaviour of stress granules. One of the genes that appeared to play a central role in the network was CDC48, which functions like VCP in yeast. In addition, many of the genes identified are involved in a process called autophagy that cells use to break down and recycle unneeded molecules, including proteins.
Working in yeast and mammalian cells, researchers showed that stress granules are cleared by autophagy, which stalled when VCP was mutated. Researchers also reported that stress granules accumulated following mutation of either CDC48 or VCP.
The research has been published in the scientific journal Cell.
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