Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are thought to belong to a spectrum of neurodegenerative disorders with sharedclinicopathological and genetic features. ALS is a fatal disease in which motor neurons in the brain and spinal cord degenerate. As the illness progresses, patients lose the ability to walk, talk and breathe. FTD is a form of dementia in which the patients primarily experience deterioration in behaviour, personality or language. Mutations in several genes have been linked to both ALS and FTD, suggesting that they have a common mechanism. However, most cases are considered sporadic. An alteration in the gene C9orf72 has recently been identified as the most common genetic cause of both ALS and FTD. However, the way in which the mutation causes neurodegenerative disease has remained unexplained until now. In this study, researchers at Emory University School of Medicine have demonstrated that this ALS/FTD mutation may be harmful because the RNA causes depletion of an important regulatory protein that binds to it RNA. The finding provides insight into the mechanism of disease in ALS and FTD, both in cases where C9orf72 is altered and in other cases. It suggests some forms of ALS/FTD may have common elements with other neurodegenerative disorders caused by noncoding repeats, such as myotonic dystrophy, spinocerebellar ataxia and fragile X-associated tremor/ataxia syndrome. It has previously been reported that the GGGGCC repeat produces RNA that is translated into an unusual protein that aggregates in cells. These protein aggregates are thought to be toxic to neurons. However, in this study, the researchers hypothesise that the GGGGCC repeat RNA itself is toxic.
