Monthly Archives: דצמבר 2015

Researchers have made a new discovery about Huntington's disease, showing that the gene that causes the fatal disorder makes an unexpected "cocktail" of mutant proteins that accumulate in the brain.

The findings are significant because these newly identified mutant proteins kill neurons and build up in regions of the brain that are most affected by the disease. The findings were published in the journal Neuron.

The researchers examined the brains of 12 deceased adult and juvenile patients with Huntington's disease. They found novel proteins that were abundant in areas of patients' brains that showed cell death, neuronal loss and other signs of disease, including neuroinflammation.

Along with a protein already implicated in Huntington's disease, the researchers found four proteins that also contribute to the disease pathology. The disease stems from a genetic mutation in the Huntingtin gene that produces too many copies of a DNA segment known as CAG, which gives rise to a longer Huntingtin protein with toxic effects. However, researchers found that this DNA repeat mutation can undergo a process known as repeat associated non-ATG (RAN) translation, producing four additional damaging repeat proteins that accumulate in the brain. This was a surprise to the researchers because these RAN proteins are made without a signal in the genetic code that was previously thought to be required for protein production. Each of the four RAN proteins contains long repeats of certain single protein building blocks, or amino acids.

Finding these novel RAN proteins in degenerated areas of the brain that were negative for the previously known mutant Huntingtin protein was crucial to linking them to the disease, said Monica Bañez-Coronel, Ph.D., a postdoctoral associate and the first author of the journal article.

Source: University of Florida

Alzheimer's patients frequently suffer from sleep disorders, mostly even before they become forgetful, and it is known that sleep plays a very important role in memory formation. Researchers have now been able to show for the first time how the pathological changes in the brain act on the information-storing processes during sleep. Using animal models, they were able to decode the exact mechanism and alleviate the impairment with medicinal agents. The study was published in Nature Neuroscience.

The sleep slow waves, also known as slow oscillations, which our brain generates at night, have a particular role in consolidating what we have learned and in shifting memories into long-term storage. These waves are formed via a network of nerve cells in the brain's cortex, and then spread out into other parts of the brain, such as the hippocampus.

The study used mouse models, which form the same protein deposits, known as β-amyloid plaques, that are visible in human patients. The scientists were able to show that these plaques directly impair the slow wave activity. The scientists also succeeded in decoding this defect at the molecular level: correct spread of the waves requires a precise balance to be maintained between the excitation and inhibition of nerve cells. In the Alzheimer models, this balance was disturbed by the protein deposits, so that inhibition was reduced.

The researchers used this knowledge to treat the defect with medication. One group of sleep-inducing drugs, benzodiazepines, is known to boost inhibitory influences in the brain. If the scientists gave small amounts of this sleep medication to the mice (approximately one-tenth of the standard dose), the sleep slow waves were able to spread out correctly again. In subsequent behavioral experiments, they were able to demonstrate that learning performance had improved as well.

Source: Technical University of Munich

JPND Board Member Dr. John Hardy of the UCL Institute of Neurology was awarded the $3 million Breakthrough Prize in Life Sciences for his pioneering research into the genetic causes of Alzheimer’s disease, other forms of dementia and Parkinson’s disease.

The Breakthrough Prize in Life Sciences honours ‘transformative advances toward understanding living systems and extending human life’. This is the first time that the prize has been awarded to a UK researcher.

Using innovative genetic analysis methods, Professor Hardy has made major contributions to the study of almost all major neurodegenerative diseases. He has published over 850 scientific papers, many of which are focused on neurological disorders and more specifically the genetics of Alzheimer’s disease. His research has underpinned nearly all basic science and treatment research into Alzheimer’s disease over the last 20 years.

“It is a great honour to be awarded the prize for our work dissecting the causes of Alzheimer and Parkinson's diseases," Hardy said. "It is, of course, our hope and aim that this understanding leads to effective treatments…I feel we can beat these diseases.”

Source: UCL