A chance to cure Alzheimer's disease

In a study on mice with an Alzheimer's disease model, the new compound anle138b reduced the severity of cognitive impairment and normalized gene expression. In addition, there is evidence that it closes defects on the membranes of nerve cells.

Alzheimer's disease is a neurodegenerative disease that affects the elderly and leads to dementia. Currently, there is no effective treatment. The disease is associated with the aggregation of beta-amyloid protein molecules that accumulate in the brain and damage neurons. The molecular processes leading to neurodegeneration are not fully understood.

According to one hypothesis, beta-amyloid aggregates are involved in the formation of membrane channels that open access for ions. Their uncontrolled movement from the intercellular space into the cell and back leads to a change in the intracellular level of ions, causes neuron dysfunction and cell death.

To test this hypothesis, researchers from Germany and the USA studied artificial membranes and membranes of living neurons. Definitive evidence could not be obtained, but the results of the study confirmed the role of beta-amyloid in the development of Alzheimer's disease.

The drug anle138b does not prevent the formation of pores on the surface of cells, but leads to changes in their conformation, thus changing the conductivity of pores. This greatly reduces and even stops the flow of ions through them.

Diagram of the cell membrane. The molecules of the drug anle138b (orange) close the unwanted holes (blue) in the membrane of the nerve cell. Source: Deutsche Zentrum für Neurodegenerative Erkrankungen (DZNE).

The drug anle138b has been investigated previously. He showed the ability to prevent the folding of certain proteins that play an important role in the development of Alzheimer's disease by attaching to protein aggregates and changing their properties. When ingested, the drug penetrates the blood-brain barrier and reaches the brain in sufficient quantities.

In the current study, anle138b was given to mice with impaired brain function and memory and the presence of amyloid plaques in the brain. The same changes are characteristic of Alzheimer's disease in humans. Anle138b improved the brain activity of mice and increased their learning ability, regardless of when treatment was started: before or after the accumulation of beta-amyloid aggregates.

The study of gene expression in the neurons of the hippocampus, the part of the brain responsible for memory, showed that in Alzheimer's disease a large number of genes did not work correctly. Treatment with anle138b significantly restored the functioning of genes and, thus, returned the normal balance of proteins. This experiment proves that the drug under study not only treats the symptoms of the disease, but is also able to influence its development.

The drug anle138b also had an effect on tau protein, another protein whose aggregates damage neurons in Alzheimer's disease. It prevented the aggregation of tau protein and inhibited the proteins accompanying this process.

It is necessary to approach the interpretation of the results of the study carefully, because none of the animal models can fully reflect the features of the course of the disease in the human body. Nevertheless, the drug anle138b can be called unique, since it affects both proteins responsible for neuronal damage: beta-amyloid and tau-protein. Based on this, it can be considered potentially effective for the treatment of other neurodegenerative diseases.

The drug anle138b should undergo clinical trials of the effectiveness of the treatment of Alzheimer's disease and possibly other neurodegenerative diseases in humans.

Article by Ana Martinez Hernandez et al. The diphenylpyrazole compound anle138b blocks Aß channels and rescues disease phenotypes in a mouse model for amyloid pathology is published in the journal EMBO Molecular Medicine.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of DZNE: Experimental Drug Interferes with Different Mechanisms Associated to Alzheimer's Disease.