ALS Treatment Target Found With Help From Yeast

Protein clumping is involved in many disorders that gradually destroy neurons in the brain such as ALS. While the cause of ALS is not known, through the use of yeast models, scientist were able to connect the protein TDP-43 to ALS by mimicking higher than normal levels of the protein in yeast. This resulted in the yeast cells dying when deadly amounts of the protein clumped in the cytoplasm. The use of yeast allowed the clumping to happen rapidly as opposed to human models where the clumping could take years.  After screening the yeast genome, the scientist found that clumping could be avoided in the yeast by blocking the production of a protein called Dbr1. They then tested the experiment in cultured human and rat neuron cells with high levels of TDP-43 and found that blocking Dbr1 production stopped the clumping of the deadly protein in these cells as well. Blocking Dbr1 causes a buildup of lariats, or “loops” of RNA left after DNA codes proteins, by not allowing Dbr1 to be produced, the lariats were not cut and recycled in the cell. The lariats “act as a sink to sequester TDP-43”. Due to the promising results of these trials scientist hope to look at the effects of blocking Dbr1 in flies, worms, and rodents and see if similar results occur.
 
This is not a problem in healthy neurons since TDP would stay in the nucleus, however in diseased people it stays in the cytoplasm.  This treatment will open up a wide variety of treatments for ALS patients that will better improve the condition of these patients. As of now treatment for ALS is minimal and the spread of the disease can range from patient to patient, through the use of this technology we could see therapies that delay on the onset of symptoms and minimize the death neurons.




http://www.medicalnewstoday.com/articles/252191.php