Huntingtons Disease

February 1st, 2013

Huntington’s disease is due to a mutation in a protein called huntingtin. U.S. scientists have discovered that two amino acids (the building blocks of proteins) in the Mutant huntingtin may be altered so that the protein is marked by normal chemical phosphorylation process so that the cell control system can delete it. Thus prevents the formation of aggregates in the neurons that cause disease. X William Yang (University of California at Los Angeles) and his team had already built a strain of transgenic mice with the mutation of the huntingtin; These mice displayed symptoms similar to the disease in humans, including problems of motor coordination, anxiety, loss of brain tissue and formation of aggregates in the neurons, typical of many neurodegenerative diseases. Have now taken one further step, checking in those mice a finding by another group of researchers that, in experiments in cell cultures, have shown how the phosphorylation prevents the formation of aggregated cell phones. Yang and his colleagues explain in the journal Neuron, through genetic engineering, have changed two amino acids of huntingtin in their mice prone to develop Huntington. A group of these animals, the genetic modification emulates permanently the phosphorylated State of two amino acids, while in another group that chemical process is prevented.

The result is striking: mice in the first group do not show symptoms of the disease and the second Yes. The researchers explain that phosphorylation is like applying chemical labels (phosphates) to amino acids of the protein. It is a natural process by which proteins are marked to play a particular role in a particular moment or also that they are destroyed by the recycling system of the cell, as a brand in a waste bucket so that garbage collectors collect. Experiments with mice and human cell cultures (this asecond work, directed by Leslie Thompson, is given to) (meet in the journal Journal of Cell biology) show that phosphorylation of only these two amino acids located at one end of the Mutant huntingtin, show it so it is destroyed and its toxic effects are avoided. It has surprised us to discover that a small change in only two amino acids of this as large protein can prevent onset of the disease!, says Yang.This points towards a new pathway to develop therapies for Huntington’s. William Yang is the Coordinator of the research. Authors have departed the existing surrounding discussion to why the huntingtin protein causes degeneration and loss of neurons. Focusing on the mutation of the huntingtin, they have taken advantage of the phosphorylation of serine 13 and 16 serine, in animal model, introducing mutations that Act on this phosphorylation in mice genetically.In particular, have replaced the 13 serine and serine 16 with aspartate fosfomimetico (SD) and alanine fosforresistente (SA). This them has allowed to find out the full mutation in the huntingtin induces deficits motors and psychiatric, aggregation of the protein and selective Neurodegeneration in SD-treated animals. In addition, they’ve observed that alterations in cases with SD have a significant impact in the process of aggregation of huntingtin mutant entirely in animal model. In the case of mutations SA this not original author and source of the article


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