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Prof. Oliver Brüstle and his team use neurons to study disease etiology

... scientists at the Life & Brain Research Center and the Clinic for Neurology at the University of Bonn have discovered a way to work around the problem. By taking skin cells from patients with a genetic movement disorder and reprogramming them into so-called induced pluripotent stem cells, researchers were able to create functional neurons that allowed them to investigate the causes of the disease. Their results will be published in the journal Nature.

The focus of the Bonn study is Machado-Joseph disease, which affects people’s ability to coordinate movement... today it represents the most frequent dominantly inherited cerebellar ataxia in Germany... The cause of the disorder is a repeating sequence in the ATXN3 gene, which causes build-up of the Ataxin protein, damaging neurons in the brain. Before the study, no one knew why the disease affected only nerve cells and what triggered the abnormal protein build-up.

“Master Cells” derived from patient skin samples

To study the disease process on a molecular level, the stem cell researcher Dr. Oliver Brüstle and his team at the University of Bonn’s Institute for Reconstructive Neurobiology derived induced pluripotent stem cells (iPS cells) from small samples of patient skin. iPS cells are cells restored to their early, undifferentiated state. Once “reprogrammed,” these “master” cells divide continuously and can transform into any cell of the body. In a subsequent step, Brüstle and his team converted iPS cells into brain stem cells, creating an ever-ready supply of neurons for their investigations.

A special feature of the neurons is that they stem from affected patients. Carrying the same genetic mutations as the patients, these neurons can serve as a cellular model for Machado-Joseph disease... The researchers showed that the formation of protein aggregate has a direct relationship with a neuron’s electrical activity. “Playing a key role is the enzyme calpain, which is activated by the increased calcium levels in stimulated neurons,” says Breuer. “This newly discovered mechanism explains why Machado-Joseph disease only affects neurons,” Brüstle explains.

Reprogramed neurons as test objects for new drugs

http://www.healthcanal.com/disorders...-disorder.html