17 August 2012

Alzheimer's disease? Stop cleaning the neurons!

Disabling the cell purification system slowed down Alzheimer's disease

RIA NewsBlocking the neuron purification system from the remnants of damaged proteins unexpectedly slowed down the course of Alzheimer's disease and, among other things, improved the cognitive abilities of mice suffering from this disease, according to an article published in the journal Science Translational Medicine (Sharma et al., Proteasome Inhibition Permits SNARE-Dependent Neurodegeneration – VM).

It is believed that Alzheimer's disease is caused by the accumulation of a pathogenic substance inside neurons, the beta-amyloid protein. This peptide is formed from the "scraps" of the APP protein, which is involved in the processes of repairing damaged neurons and forming long-term connections between them. Violations in the processing of old molecules of this protein lead to the appearance of beta-amyloid plaques and the destruction of nerve cells.

A group of biologists led by Thomas Sudhof from Stanford University (USA) observed the process of removing fragments of beta-amyloid from nerve cells, experimenting with drugs that enhanced or suppressed the neuron purification system.

"According to the current generally accepted ideas in neurophysiology, we should try to accelerate the removal of fragments of damaged proteins from the nerve cells of the brain of people suffering from Alzheimer's, Parkinson's or Huntington's diseases, and not hinder it," Sudhof explained.

Biologists raised a population of mice suffering from genetic defects that inevitably led to the development of neurodegenerative diseases. When their wards began to show the first signs of Alzheimer's disease, scientists divided the rodents into several groups and began to regularly inject drugs into their blood that block or accelerate the processing of proteins.

To the surprise of scientists, the greatest positive effect was provided by two substances – lactacystin and epoximycin, suppressing rather than enhancing the effect of the neuron purification system. Having received such an unexpected result, Sudhof and his colleagues tried to understand the cause of this phenomenon by tracing the cellular mechanisms affected by lactacystin and epoximycin.

It turned out that these compounds enhance the work of the protein complex SNARE (soluble N-ethylmaleimide–sensitive factor attachment protein receptor, and into Russian, if you want, translate yourself – VM) – a combination of several proteins with which neurons connect to each other and exchange chemical signals. Drugs that enhance the work of the cell purification system from protein fragments block the synthesis of these complexes, which negatively affected the mental health of rodents.

According to Sudhof and his colleagues, the brains of people who have died from Alzheimer's disease contain a very small amount of SNARE proteins. This means that suppressants of the purification system can be used to slow down the course of Alzheimer's disease, albeit with significant side effects.

"As in the case of cancer treatment, in a situation where an important protein is destroyed by the cell purification system, which has an extremely negative effect on human health, the potential benefits of suppressing its activity may outweigh the side effects," the biologists conclude.

Portal "Eternal youth" http://vechnayamolodost.ru17.08.2012

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