Chemical "switch" of neurodegeneration
Researchers at the University of Montreal, working under the guidance of Dr. Alex Parker, in experiments on roundworms identified and blocked a chemical cascade of reactions that triggers the development of neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis and dementia.
This finding is of particular importance for patients with Huntington's disease, a lethal genetic disease that usually manifests in middle age and leads to progressive death of certain regions of the brain. The main sign of this disease is the accumulation of aggregates of abnormally altered huntingtin protein in brain cells. To date, Huntington's disease is incurable, and existing therapies provide only a slight improvement.
The authors decided to find out whether TDP-43 and FUS proteins, which are part of protein aggregates characteristic of Huntington's disease and other neurodegenerative diseases, play any role in the toxicity of the mutant form of huntingtin or are only harmless by-products of the pathological process. To do this, they used a simple genetic model based on the expression of a mutant form of huntingtin in the cells of the nervous system of the roundworm C.elegans.
It turned out that the removal of genes encoding the TDP-43 and FUS proteins reduced the severity of neurodegenerative changes caused by the accumulation of the mutant form of huntingtin. The authors were able to reproduce the results obtained on mammalian cell culture. Further experiments showed that the removal of the chemical compound progranulin from the brain of worms or cells, which is the target of TDP-43, significantly increased the toxicity of huntingtin, while increasing its concentration suppressed the death of neurons.
According to the results of earlier studies, progranulin is extremely important for the survival of brain cells, and a decrease in its concentration is involved in the development of various forms of dementia. The researchers plan to continue studying the relationship they have identified using more complex biological models. They believe that if the identified mechanisms also work in mammalian cells, progranulin therapy will delay the manifestation or slow down the progression of Huntington's disease in humans.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Montreal:
Researchers find chemical “switches” for neurodegenerative diseases.
28.11.2012