A micro-RNA as a key regulator of learning and Alzheimer's disease

September 23, 2011

Göttingen, September 23rd, 2011. Proteins are the molecular machines of the cell. They transport materials, cleave products or transmit signals - and for a long time, they have been a main focus of attention in molecular biology research. In the last two decades, however, another class of critically important molecules has emerged: small RNA molecules, including micro-RNAs. It is now well established that micro-RNAs play a key role in the regulation of cell function."A micro-RNA regulates the production of an estimated 300-400 proteins. This class of molecules can be regarded as a switch that coordinates the transition of cells from one state to another," explains Prof. Dr. André Fischer, scientist at the German Center for Neurodegenerative Diseases (DZNE) and Speaker of the DZNE site Göttingen. He and his team have identified a micro-RNA that regulates the learning processes and probably plays a central role in Alzheimer's disease. The researchers have shown that there is too much of a micro-RNA called "miRNA 34c" in mouse models of Alzheimer's disease, and decreasing the level of miRNA 34c in these mice can restore their learning ability. The scientists have identified a new target molecule that might be important for diagnosis and treatment of Alzheimer's disease. The studies were carried out in collaboration with scientists at the European Neuroscience Institute Göttingen, the Göttingen University, the DZNE site in Munich and researchers from Switzerland, USA and Brazil.

miRNA 34c was identified using a highly complex method called "massive parallel sequencing". With this technology, Fischer and his colleagues captured the complete RNA composition in the hippocampus - the learning region of the brain - and compared this with the RNA of the entire brain. They showed that miRNA 34c is enriched in the hippocampus, especially in during the time window of a few hours after a learning phase. "We suspect that the function of micro-RNA 34c is to switch off a whole range of gene products that are turned on in the learning process," Fischer said. Too much miRNA 34c would then lead to a blockade of learning - which is exactly what was shown in subsequent experiments. In old mice, which do not learn as easily as their younger counterparts, there was indeed too much miRNA 34c. The miRNA-34c level was also elevated in mice that are used as specific research models of Alzheimer's disease. These mice carry a genetic mutation that can cause Alzheimer's in humans and show disturbances of memory function. Moreover, miRNA 34c seems to not only play a role in mice. Fischer and his colleagues showed these levels are also elevated in the brains of Alzheimer's patients.

In further mouse experiments, the researchers showed that miRNA 34c is actually causally involved in the pathogenesis of Alzheimer's disease and memory disorders. An artificial increase of miRNA-34c level in normal mice results in memory impairment in the animals. Secondly, as Fischer and his colleagues have shown, lowering miRNA-34c levels can restore learning ability in mouse models of Alzheimer's disease and in older mice. "Neurodegenerative diseases like Alzheimer's are associated with many factors. We hope that with the identification of micro-RNA 34c, we have found an important mediator of pathogenesis," says Fischer. "Micro-RNA 34c would then be a good candidate for the development of drugs against Alzheimer's."
-end-
Original publication: Athanasios Zovoilis, Hope Y Agbemenyah, Roberto C Agis-Balboa, Roman M Stilling,Dieter Edbauer, Pooja Rao, Laurent Farinelli, Ivanna Delalle, Andrea Schmitt, Peter Falkai, Sanaz Bahari-Javan, Susanne Burkhardt, Farahnaz Sananbenesi1 & Andre Fischer. Micro-RNA-34C is a novel target to treat dementias. EMBO J advance online publication 23 September 2011; doi:10.1038/emboj.2011.327

Contact information:
Prof. Dr. André Fischer
German Center for Neurodegenerative Diseases (DZNE)
c/o Department of Psychiatry and Psychotherapy
University Medical Center
Georg-August-University Göttingen
Tel.: +49 (0) 551 / 3910378
Email: andre.fischer@dzne.de

Dr. Katrin Weigmann
Public Relations Department
German Center for Neurodegenerative Diseases (DZNE)
Tel.: +49 (0) 228 / 43302-263
Mobile: +49 (0) 173 / 5471350
Email: katrin.weigmann@dzne.de

Helmholtz Association

Related Neurodegenerative Diseases Articles from Brightsurf:

Bringing drugs to the brain with nanoparticles to treat neurodegenerative diseases
Researchers from the Institut national de la recherche scientifique (INRS) have shown that nanoparticles could be used to deliver drugs to the brain to treat neurodegenerative diseases.

First 'pathoconnectome' could point toward new treatments for neurodegenerative diseases
Scientists from the John A. Moran Eye Center at the University of Utah have achieved another first in the field of connectomics, which studies the synaptic connections between neurons.

Unlocking the mystery of tau for treatment of neurodegenerative diseases
A team of researchers from various collaborating universities and hospitals in Japan has uncovered crucial molecular details regarding the activity of the ''tau'' protein, promising to revolutionize the therapy of tau-induced neurodegenerative diseases.

Investigational drug stops toxic proteins tied to neurodegenerative diseases
An investigational drug that targets an instigator of the TDP-43 protein, a well-known hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), may reduce the protein's buildup and neurological decline associated with these disorders, suggests a pre-clinical study from researchers at Penn Medicine and Mayo Clinic.

Inhibition of sphingolipid metabolism and neurodegenerative diseases
Disrupting the production of a class of lipids known as sphingolipids in neurons improved symptoms of neurodegeneration and increased survival in a mouse model.

How understanding the dynamics of yeast prions can shed light on neurodegenerative diseases
How understanding the dynamics of yeast prions can shed light on neurodegenerative diseases

New family of molecules to join altered receptors in neurodegenerative diseases
An article published in the Journal of Medicinal Chemistry shows a new family of molecules with high affinity to join imidazoline receptors, which are altered in the brain of those patients with neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's.

Examining diagnoses of stress-related disorders, risk of neurodegenerative diseases
Researchers investigated how stress-related disorders (such as posttraumatic stress disorder, adjustment disorder and stress reactions) were associated with risk for neurodegenerative diseases, including Alzheimer and Parkinson disease and amyotrophic lateral sclerosis (ALS), using data from national health registers in Sweden.

Toxic protein, linked to Alzheimer's and neurodegenerative diseases, exposed in new detail
The protein tau has long been implicated in Alzheimer's and a host of other debilitating brain diseases.

Study uncovers unexpected connection between gliomas, neurodegenerative diseases
New basic science and clinical research identifies TAU, the same protein studied in the development of Alzheimer's, as a biomarker for glioma development.

Read More: Neurodegenerative Diseases News and Neurodegenerative Diseases Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.