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Wednesday, 14 September 2016 12:18

Parkinson research: Therapy Development with yeast cells

Basic researchers from Excellenzcluster CNMPB in Göttingen led by Prof. Gerhard Braus use yeast cells to study cellular mechanisms of Morbus Parkinson. They got new insights about pathogenic processes.

The scientist team from CNMPB (Cluster of Excellence and DFG Research Centre for Microscopy in Nanometer Scale and Molecular Physiology of the Brain of the University Medicine Göttingen) analysed a complex mechanism which is essential for the cell mortality during Parkinson's. Moreover, they identified a factor with a neuro-protective effect on human nerve cells.

α-Synuclein is a small solvable protein which adjusts the release of dopamine in the brain. There is more α-Synuclein in patients´ nerve cells suffering from Parkinson's nerve cells than in healthy cells. A surplus of this protein causes cell depositions typical for the disease. For some time, scientists investigate the biochemical modifications of the protein α-Synuclein.

It is known, that a phosphorylation (attachment of a phosphate group) of this protein has a protecting effect, whereas a nitration (attachment of a nitrogen oxide) has a damaging one. However, the complete process is more complicated. (A review of the Constance University gives an overview.

In their Parkinson yeast model they observed, that a tyrosine nitration, i.e. the biochemical attachment of nitrogen molecules (NO2) to an amino acid of the α-Synuclein, led to toxic aggregates composed of this α-Synucleins. Moreover, the cell organelles (mitochondria) fragmented which are responsible for energy supply. As a result the growth of the yeast cells was strongly limited.

However, the nitration promotes the interaction of α-Synuclein molecules. On the other hand, the emerging robust α-Synuclein dimer had a protecting effect followed by a lower mortality rate of the cells. Interestingly, the positive effect of dimer building were only able to diminish the neuro-toxic effect of a nitration but not equalize, as is said in the researchers press release.

Further information on the subject in the original publication:

Kleinknecht A, Popova B, Lázaro DF, Pinho R, Valerius O, Outeiro TF, Braus GH (2016): C-terminal Tyrosine Residue Modifications Modulate the Protective Phosphorylation of Serine129 of a α-Synuclein in a Yeast Model of Parkinson’s Disease. PLOS GENETICS, 12(6): e1006098. doi:10.1371/journal.pgen.1006098