Huntington’s disease is caused by a mutation in a protein called Huntington. U.S. scientists have found that two amino acids (the building blocks of protein) of mutant huntingtin can be altered so that the protein be marked by normal chemical process of phosphorylation for the control system of the removed cell. It thus prevents the formation of aggregates in neurons that cause the disease. X. William Yang (University of California at Los Angeles) and his team had already built a line of transgenic mice with the mutation of huntingtin, these mice show symptoms similar to human diseases, including motor coordination problems, anxiety, loss of tissue Brain aggregate formation in neurons, typical of many neurodegenerative diseases. They have now gone a step further, ensuring that those mice a finding from another group of researchers who, in cell culture experiments have shown how phosphorylation prevents the formation of cellular aggregates. Yang and colleagues explain in the journal Neuron that through genetic engineering, have changed two amino acids of huntingtin of mice prone to develop Huntington.
In a group of these animals, genetic modification emulates permanently phosphorylated state of the two amino acids, whereas in the other group that prevents chemical process. The result is convincing: the first group of mice showed no symptoms of the disease and the latter itself. The researchers explain that phosphorylation is like sticking labels chemical (phosphate) to the amino acids of the protein. It is a natural process by which proteins are marked to play a certain role at a particular time or even to be destroyed by the recycling system of the cell, as a mark in a waste receptacle for garbage pick you up. Experiments with mice and in cultured human cells (this asegundo force, led by Leslie Thompson, is given announced in the Journal of Cell biology) show that phosphorylation of only these two amino acids located at one end of the mutated huntingtin, the point to be destroyed and prevents its toxic effects. “We were surprised to discover that a small change in only two amino acids of this protein as large can prevent the onset of the disease!, Says Yang.” This points to a new way to develop therapies for Huntington. “William Yang is the focal research.
The authors have left the existing debate about why the altered Huntington’s protein causes degeneration and loss of neurons. Focusing on polyglutamine mutations, have used the phosphorylation of serine 13 and serine 16 for, in animal model, introduce mutations that act on this phosphorylation in mice genetically modificados.En particular, have replaced serine 13 and serine 16 with aspartate fosfomimetico (SD) and alanine fosforresistente (SA). This has allowed ascertain that the mutation in huntingtin induces motor deficits and psychiatric disorders, protein aggregation and selective neurodegeneration in animals treated with SD. They have also observed that alterations in patients with SD have a significant impact on the process of aggregation of mutant Huntington’s completely animal model. In the case of SA mutations do not.