Kayla's article: Huntington's Disease

Huntington's disease, a dominant disease that causes people to lose control over voluntary movements, is soon to have a cure. Scientist have found the main gene that causes this disease, it is a neurodegeneration condition, and it affects thousands in the United States. Its protein is called huntingtin (Htt); when mutated, scientist found out that it malfuntions and kills neurons. Here are three of the many disruptions this mutant Htt causes: interfering with normal gene activity patterns, the transport of proteins needed for nerve cell maintenance, and overwhelming cells with toxic (calcium ions). Researchers everywhere are excited, they are finding drugs that have potential for this neuronal problem caused by Htt.

Researchers are using mice models to help find how mutant Htt causes the brain degeneration of this disease. At the beginning of the mutation there is a string of the amino acid glutamine that contains thirty-six or more glutamine. A normal version of Htt only contains from six to thirty-five. With that many glutamines in protein it produces up to nine genes and causes the neurodegenerative disease; scientist are still trying to get a better understanding of ths event. There are clumps or abnormal deposits of the mutant Htt near other protein being found in brain tissue of Huntington's patients that flow along the long axonal projectios which causes toxicity. Then there are enzymes splitting from protein that attaches to Htt and release another toxic (N-terminal fragments) into the brains of the Huntington's patients, but N-terminal fragments are not toxic in normal humans. Potential therapy is offered by the enzymes with its inhibitors because it can scientificly decrease the toxicity of mutant Htt in Huntington's patients (mice).

Scientists are all agreeing that N-terminal fragments of mutant Htt are toxic, there is then the aggregates that kill the neurons or protect other cells from the mutant Htt's toxic. But the aggregates can be harmful and it shows that to reduce toxicity of mutant Htt, the aggregates restrain their formation. Then there is a drug called rapamycin that decreases Htt aggregation, and the toxicity in cultured neurons by stimulating autophagy; which cells use to get rid of useless proteins. Lysosomes also help in the process and by clearing this does not keep it under control for long. All researchers have their opinion whether or not Htt aggregation is harmful because they have found that lab mice neurons die even with the lack of Htt inclusions. If the neurons have the inclusions there is a better chances of survival than those without it; with a lot of inclusions show no signs of neurodegeneration.

Ignoring the fact that all forms of mutant Htt is toxic, remember the extra glutamines that cause problems in the protein. An example would be in the nerve cells for the gene activity. This is because Htt joins protein that control gene expression which is part of the cell's gene regulatory machinery. Researchers say that the mutant N-terminal fragments of Htt affects the regulatoey machinery: by not letting the Htt to join with the transcription factor. When this happens it can not do its job, and prevent factors from using certian genes. Binding to and restraining a histone acetylase, which is an enzyme that marks genes for activity, happens indirectly to a genes expression from a mutant Htt, causing another way of decreasing Htt's toxicity.

Then there are treatments that restrain the enzymes that will remove acetyl groups from histone to slow down the the neurodegeneration called sodium butyrate. And researchers are also finding that the mitochondria, produces cell energy, will malfunction causing neuronal damage from the mutant Htt. There is also the p53 that controls several genes and the mutant Htt binds to the transcription factor which affects the mitochondria. Scientist showed that by inactivating the p53 gene prevents malfunctioning of the mitochondria. Molecules need to be found to block the p53 mutant Htt or slow down the energy produced from the mitochondria. Then there is the medium spiny neurons that are to be the first to degenerate in Huntington's disease, and these neuronsexperienced a greater take of calcium ions which cause them to die. These receptors where glutamine exerts are possible starts for the disease's therapies. Finally there is the normal Htt that needs protection because they supply brain-derived neurotrophic factors which cells need to survive. Usually Huntington's disease shows up in the patient's forties, and scientist are now closer to finding the most effective treatments.

What I think is interesting is how far and close the scientist are to finding a treatment, they have practically found what causes this disease. Now they just need to put all the little pieces together and find the right drug. It is all most like cancer in a way because it takes awhile to develop and when it does it is very hard to control. It is also amazing that there is a list of so many potential drugs for this disease that you would think that if you could just mix a little of each together and find the cure. But it is not that simple it's comlpex just like God who allowed this disease to exist.