May 26, 2009 - Researchers at ANSTO have discovered that a protein, Alpha-Synuclein, which plays a role in the development of Parkinson’s disease when it behaves abnormally, can be controlled with a man-made polymer, dendrimer, also known as a ‘dense star’ polymer.
ANSTO Researcher, Dr Agata Rekas, said that past research had shown the dendrimer – called a PAMAM dendrimer and made by Dendirtech Inc - had positively affected a peptide involved in Alzheimer’s disease (ABeta) and a prion peptide. So Dr Rekas and Dr Seok Il Yun, an ANSTO Post Doctoral fellow, decided to see if it had a similar effect on Parkinson’s disease, which affects around one in 250 Australians.
“As all these diseases affect the brain and neuronal pathways in the body we anticipated the dendrimer’s effect would be similar, and we were right,” said Rekas.
“The Alpha-Synuclein protein is a natural protein in the body but when it aggregates into fibrils, long insoluble strings of protein molecules stuck together, it affects transmissions to the brain, resulting in Parkinson’s disease,” Dr Rekas said. “No one is sure of the protein’s normal role but we believe it assists cognitive function.
“It is thought that the aggregation is triggered by a dopamine3 deficiency and causes deposits in the brain to occur, however this could be just a factor, not the complete cause, of the disease,” she said. “There is still much to find out, but it’s all part of the puzzle. The exciting part of our results is that it most definitely provides further information as to how this dendrimer can contribute to developing better therapeutics for Parkinson’s disease,” she said.
A dendrimer is spherical in shape and contains chemical groups similar to those of proteins, which start branching out in the middle so the dendrimer increased in size as each layer was added, similar to the branch-like structures seen in snow flakes.
“The more layers in the dendrimer the more effective it was due to the larger surface area. In the experiments we put certain amounts of these dendrimers and a control, with no dendrimers, into a protein solution for over 120 hours and stimulated aggregation with heat and shaking,” she explained. “The control measured a lot of fibrils and different dendrimers reduced this fibrillar growth to various extents.
“We used an electron microscope to look at what was physically happening and verified the results using small angle neutron scattering, where a neutron beam passes through the sample onto a detector giving information as to what’s occurring at the molecular level," she said.
“The results clearly showed that the larger dendrimer inhibited the abnormal activity of the protein best. This information can now be used by drug companies focussed on treating Parkinson’s so the next stage would be for such companies to develop this research further,” said Rekas.