Important associations between genetics, sleep behavioridentified by study

               In the article, “Important associations between genetics, sleep behavior identified by study,” from Science Daily talks about identifying the genes that are associated with sleep duration and validating the connection between sleep and lifestyle factors, including but not limited to age, gender, and exercise. Coriell Institute for Medical Research performed an analysis concerning genes involved in ATP metabolism, circadian cycles, narcolepsy, sleep cycles in mice, and bear hibernation. I thought this was a very important topic, especially because I do not have a great sleeping schedule. Everyone knows that getting inadequate sleep is a major problem and can result in many health complications.

                One quotation about the results of the study by Dr. Scheinfeldt states, "Individuals who average six hours or less are more susceptible to adverse health issues, and we found that participants enrolled in the CPMC study vary greatly in the amount of sleep they receive. Effectively, by learning more about an individual's sleep patterns and considering environmental and genetic risk factors, physicians may one day be able to identify risks before they occur and target health solutions."

                The 2007 study had 8, 500 volunteer participants and produced more than 20 publications examining a wide range of human conditions such as cancers and diabetes. From the outcome of this study, it is apparent that genes have a major impact on sleep. The result of sleep deprivation are many human conditions that are harmful to organisms. 

"Identification of the Antineoplastic Agent 6-Mercaptopurine as an Activator of the Orphan Nuclear Hormone Receptor Nurr1"

In a 2003 publication by Peter Ordentlich, Yingzhuo Yan, Sihong Zhou, and Richard A. Heyman, the role of Agent 6- Mercaptopurine, commonly known as the drug 6-MP, was studied in relation to the protein Nurr1. Nurr1 is encoded by the NR4A2 Gene. 6-MP is used for many diseases, including Crohn's Disease, in an attempt to reduce inflammation. It was demonstrated that the regulation of the transcriptional activity of Nurr1 by 6-Mercaptopurine can be inhibited by certain factors in the purine biosynthesis pathway. This lends to the possibility of Nurr1 interfering with the antiproliferative effects of 6- MP. One of the ways that the specific effects of 6- MP on Nurr1 was tested was by using other nuclear hormone receptors for comparison, specifically LXR, FXR, RXR, ER, and ROR, which did not show activation for up to 50 microM. 

Understanding the receptor function of Nurr1 is critical due to the fact that Nurr1 may lead to the expression of inflammatory hormones. It was also found that the 6-MP effect was not dependent on the ligand-binding domain. 6-MP seemed to be specific to Nurr1 in that other compounds with a similar mechanism do not activate Nurr1. Additionally, it was discovered that the level of adenine, adenosine, or guanosine molecules affect Nurr1. The reduction of adenosine molecules resulted in less of ATP, suggesting that there is an ATP-dependent pathway. When this pathway is blocked, the transcriptional activation occurs. By modifying the mechanism of 6-MP, new findings can be generated on the methods used to regulate Nurr1. 

It is interesting but not surprising that a protein could involve so much complexity in the way of treating diseases such as Crohn's Disease, which can infect the entire gastrointestinal tract in a human body. It is important to try and modify drugs to target certain proteins and therefore possibly result in the expression of particular genes. Crohn's Disease can result in bleeding, pain, and weight loss. 

Links: 

http://www.jbc.org/content/278/27/24791.full.pdf+html?sid=dcdef3a7-3fcc-43e3-8808-fcc7d1719254

http://www.genecards.org/cgi-bin/carddisp.pl?gene=NR4A2

http://www.ccfa.org/resources/maintenance-therapy.html?referrer=https://www.google.com/