Mutations in the p63 protein cause a large number of diseases. The most serious is Hay-Wells syndrome. The scientists of Goethe University and Federico II of Naples have discovered new details on the genetic cause of the disease. It seems that the syndrome is much more similar to Alzheimer's and Parkinson's than to other syndrome related to p63. The discovery could help develop new possible treatments.

The p53 protein has the task of suppressing any tumors. Its malfunction is one of the first stages of cancer development. It is also the cause of a series of syndromes characterized by defects in embryonic development. The transcription factor p63, on the other hand, regulates the development and proliferation of stem cells. Some of its mutations lead to very serious diseases, including Hay-Wells syndrome.

The roots of the Hay-Wells syndrome reside in two domains of the p63 protein, completely unrelated to those related to other diseases originating from p63. These domains are a platform for protein interactions. For a long time it was therefore assumed that the problem was in the loss of these interactions. In reality it is not like that.

The mutations inside p63 expose the sequences of hydrophobic amino acids and push them to bind to each other. In this way a large complex without a structure is formed, which causes the loss of the functions of p63. Aggregates are similar to those that cause other diseases, such as Parkinson's and Alzheimer's.

Source: goethe-university-frankfurt.de

Researchers at the University of Washington in St. Louis have discovered a molecular factor that causes Primary Ciliary Dyskinesia. Those suffering from this disease have a genetic abnormality that causes the malfunctions of the vibratile cilia of the respiratory mucosa to malfunction. Until now, however, it was unclear how this anomaly translates into the symptoms of the disease.

The vibrating cilia of the respiratory mucosa serves to free the respiratory tract from excess of mucus. In those suffering from Primary Ciliary Dyskinesia, the eyelashes do not work. In fact, a genetic mutation prevents the proper production of the lily-forming proteins. It would all seem very simple, if it were not for some people to have flaws in proteins untied by eyelashes. In these cases, it was not clear how the genetic anomaly and defective proteins translated into symptoms.

According to the study, the three apparently unconnected non-functioning proteins are actually fundamental. They are in fact the elements that hold together the whole mechanism of eyelashes. When all is well, they form a scaffold on which the molecular motor of the eyelashes is installed. When they do not work they do not even work the eyelashes, although apparently everything is fine.

The researchers observed the eyelashes of some patients with this type of anomaly. The malfunctioning of the three "scaffolding" proteins made the structure unstable and hindered the development of eyelashes.

Source: medicine.wustl.edu

Rett's syndrome is a devastating genetic disease. Causes disorders at the motor level and behaviors of the autistic mold. The researchers at Case Western Reserve University School of Medicine have perhaps found a solution. In fact, they are working to restore brain function and regress at least part of the symptoms. One method in particular seems to have worked on some animal models.

The researchers found that the prefrontal cortex plays an important role in some cognitive and respiratory abnormalities. In the guinea pigs with the genetic defect due to Rett's syndrome, this area was almost inactive. In fact, it lacked adequate stimulation from other nerve cells. According to the researchers, this poor activity could be the cause of some symptoms of Rett syndrome.

To test their hypothesis, the scientists activated the prefrontal cortex neurons. The mice treated in this way began to breathe normally. They also recovered some of the long-term memory. A molecule was enough to almost completely eliminate the most severe symptoms of Rett syndrome in mice. Once normal activity was restored, the brain was relatively healthy and the guinea pigs showed a marked improvement.

This is a first discovery, but it also suggests a possible treatment for human beings. Furthermore, the same procedure could also be applicable to other brain regions. It could therefore benefit both those suffering from Rett's syndrome and those suffering from a disease of the same spectrum.

Source: case.edu