Discovery Aids Understanding Of ALS

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ALS cells

March 19th, 2018

An international team of neuroscientists and researchers, including those from the Hebrew University of Jerusalem, have discovered a basic molecular mechanism that sheds light on the disease process underlying amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease.

This basic science could aid the development of new therapies for the crippling disease, which prevents the brain from being able to communicate with muscles, eventually causing paralysis and premature death.

The findings, which are published in the journal Brain, are the result of the research that began eight years ago when investigating the effect on various molecules when TDP-43, a protein, is removed from the cell nucleus. TDP-43 binds to cellular RNA and is central to the pathology involved in ALS. One type of RNA binding proteins, hnRNP A1, caught their eye, because there is a second form rarely mentioned in literature.

On binding to RNA, TDP-43 can alter how it is spliced – a process referred to as alternative splicing. The current study showed that TDP-43 binds hnRNP A1 pre-mRNA and modulates its splicing. This is important for understanding ALS because TDP-43 is known to be a key component of non-living substances in cells called cytoplasmic inclusions, which are seen in 97% of ALS cases.

The data showed that when TDP-43 is either absent altogether or just absent from the nucleus, the splicing pattern of hnRNP A1 is altered, suggesting that the spectrum of RNA metabolism mis-regulation is much broader than previously thought.

While studies such as this do not immediately give rise to new ALS treatments, they do provide a deeper understanding of this complicated disease. This type of work provides important information for future drug targets and the development of biomarkers aimed at detecting the disease more rapidly and following its progression.

 

Read source article:
Discovery aids understanding of amyotrophic lateral sclerosis

 

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