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New details uncovered about the genetic cause of ALS.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells responsible for controlling voluntary muscles.  The disease doesn’t usually  impair a person’s mind or intelligence, however, several recent studies suggest that some patients with ALS may have depression or alterations involving decision-making and memory.  The cause of ALS is not known, and it is still unclear as to why ALS strikes some people and not others.  Now, researchers from the University of Toronto state they have discovered new details about a key gene involved in ALS.

In this fatal disorder with no effective treatment options, researchers achieved a major breakthrough in 2011 when they discovered mutations in the gene C9orf72, as the most frequent genetic cause of ALS and frontotemporal dementia. However, little was known about how this gene and its related protein worked in the cell.

To investigate this the current study used novel antibodies that not only specifically detected C9orf72 in human tissues, it also distinguished between both the long and short isoforms.  The team state that by using these antibodies they have made the remarkable discovery that C9orf72 is localized to the nuclear membrane in healthy neurons, and is mislocated to the plasma (outer membrane) in diseased neurons.

The results showed that C9orf72 directly interacts with components of the nuclear shuttling complex, which is responsible for the movement of proteins across the nuclear membrane. The data findings show that one such protein is TDP-43, which normally resides in the nucleus and is wrongly localized to the cytoplasm in diseased neurons in ALS. The team state that TDP-43 accumulation and aggregation in the cytoplasm diagnoses most ALS cases, however, the link with C9orf72 was absent.

Now through the use of the C9orf72 antibodies the lab state they have found that loss of C9orf72 from the nuclear membrane correlates with TDP-43 pathology. These results suggest that defects in C9orf72 affect the proper functioning of the nuclear shuttling complex, resulting in TDP-43 build up in the cytoplasm.

The researchers surmise that they have discovered a link between the genetic cause of ALS and its pathology that appears to be important for all cases, not just familial ones.  They go on to conclude that the possible involvement of C9orf72 in the shuttling between nucleus and cytoplasm opens intriguing new avenues of research into the causes of ALS, and hopefully, one day an effective treatment or cure.

Source:  University of Toronto

 

Uncovering a key relationship in ALS  - neuroinnovations

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Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.

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An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.

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