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

Source:
https://www.med.uni-goettingen.de/de/content/presseinformationen/presseinformationen_24962.asp