29 September 2011

Memory disorders, Alzheimer's disease and microRNA

microRNA as a key regulator of learning ability and Alzheimer's diseaseLifeSciencesToday based on DZNE materials: A micro-RNA as a key regulator of learning and Alzheimer's disease

For many years, the focus of molecular biologists has been on molecular cellular machines – proteins. However, over the past two decades, another class of vital molecules has emerged – small RNAs, including microRNAs (micro-RNAs). It is now well known that microRNAs play a key role in regulating cell function.

The length of a microRNA gene is equal to one hundredth of the length of a typical gene encoding matrix RNA (mRNA). Matrix RNA is responsible for the assembly of proteins. microRNA genes can control the most important process of protein assembly by encoding a short chain of microRNA that binds to mRNA and effectively blocks synthesis.

"It is estimated that microRNAs regulate the synthesis of 300-400 proteins. This class of molecules can be considered as a switch that coordinates the transition of a cell from one state to another," explains Professor André Fischer, researcher at the German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen, DZNE).

Professor Fischer and his group have identified microRNAs that regulate learning processes and probably play a central role in the development of Alzheimer's disease. Using a model of this disease reproduced in mice, scientists have shown that there are too many microRNAs in the brains of such animals, called miRNA 34c, and a decrease in the level of this microRNA restores their ability to learn. Thus, a new molecular target has been identified that can be used for the diagnosis and treatment of Alzheimer's disease. The study was conducted in collaboration with scientists from the European Neuroscience Institute Göttingen, the University of Göttingen (Georg-August-Universität Göttingen), the Munich Department of DZNE, as well as with researchers from Switzerland, the USA and Brazil.

miRNA 34c was identified using a high-tech method called mass parallel sequencing. Professor Fischer and his colleagues determined the complete composition of RNA in the hippocampus – the brain region associated with learning and long–term memory - and compared it with the RNA of the entire brain. The level of miRNA 34c in the hippocampus was elevated, especially within a few hours after the learning phase.

"We assume that the function of microRNA 34c is to suppress the synthesis of a number of proteins occurring in the learning process," says Professor Fischer. "Therefore, too much microRNA 34c leads to learning blocking, which is exactly what was shown in subsequent experiments."

In the brains of old mice, whose learning is noticeably slower than that of young animals, there is indeed much more microRNA 34c. microRNA 34c levels were also elevated in mice with an Alzheimer's disease model. For such mice carrying a genetic mutation that leads to the development of Alzheimer's disease in humans, memory impairment is characteristic.

According to scientists, microRNA 34c play a similar role in the human body. Professor Fischer and his colleagues have shown that the levels of this microRNA are also elevated in the brains of patients with Alzheimer's disease.

In subsequent experiments on mice, scientists have shown that microRNA 34c is indeed involved in the pathogenesis of Alzheimer's disease and memory disorders. Artificially increasing the level of microRNA 34c in normal mice leads to memory impairment. At the same time, a decrease in their level restores the ability to learn in mice with an Alzheimer's disease model and in old animals.

"Neurodegenerative diseases, such as Alzheimer's disease, are associated with many factors. We hope that with the identification of microRNA 34c, we have found an important intermediate in the pathogenesis of this disease," says Professor Fischer.

In his opinion, microRNA 34c is a good candidate for the role of a molecular target of new drugs for the treatment of Alzheimer's disease.

The article by Zovoilis et al. microRNA-34c is a novel target to treat dementias published in The EMBO Journal.

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