10 December 2009

How to protect neurons from Alzheimer's disease

Researchers at the Gladstone Institute of Neurological Diseases have identified drugs that can normalize the development of new neurons in the adult brain even in the presence of beta-amyloid (Aß) and apoliprotein E4 (ApoE4) proteins, which are the main causes of Alzheimer's disease.

For a long time it was believed that nerve cells do not recover, but now the brain's ability to form new neurons throughout the life of the body is a proven fact. One of the regions of the adult brain that retain the ability to generate new cells is the hippocampus, which is involved in learning and memorization processes and seriously suffers from Alzheimer's disease.

A group of scientists led by Dr. Li Gan studied the development of neurons formed in the hippocampus of adult genetically modified mice, in the brain of which there is a production and accumulation of a large amount of human beta-amyloid. To the surprise of the researchers, it turned out that beta-amyloid initially stimulates the formation of new neurons, but at later stages greatly disrupts the process of their maturation.

The authors also found that the effect of compounds suppressing the activity of receptors to the neurotransmitter gamma-aminobutyric acid (GABA) at the early stages of neuron development, or the activity of the calcineurin protein at the late stages of development, thereby enhancing the mechanisms of transmission of nerve impulses mediated by glutamic acid, normalizes the development of neurons from stem cells even in conditions of increased concentrations of beta-amyloid. After analyzing the results obtained, they suggested that the neurogenesis disorder is based on an increase in the activity of GABA-mediated pulse transmission processes induced by beta-amyloid, or an imbalance between the activity of gamma-aminobutyric and glutamic acids.

In parallel work, researchers working under the guidance of Dr. Yadong Huang studied apoliprotein E4, which is the main genetic risk factor for Alzheimer's disease. Scientists used genetically modified mice to study the effect of various variants of human apoliprotein E4 on the maturation of progenitor cells that give rise to new neurons in the adult brain. They found that ApoE4 also disrupts the development of young neurons in the hippocampus and identified compounds blocking this effect. In this case, drugs that enhance the activity of GABA-mediated signal transmission processes had a beneficial effect on the maturation of neurons.

Despite the fact that the use of cell therapy methods for the treatment of Alzheimer's disease is a matter of the distant future, experts believe that these two works point to strategies that will help overcome difficulties on the way to achieving this goal. The results obtained by the authors clearly demonstrate the possibility of using pharmacological drugs to improve the development of neurons in the memory centers of the adult brain, even in the presence of toxic factors that are considered to be the cause of the development of Alzheimer's disease.

The results of the work were published in the December issue of the journal Cell Stem Cell in the articles "Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease" and "GABAergic Interneuron Dysfunction Impairs Hippocampal Neurogenesis in Adult Apolipoprotein E4 Knockin Mice".

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on ScienceDaily: Strategies to Protect New Brain Cells Against Alzheimer's Disease.


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