Point at which Parkinson’s-related proteins become toxic identified
Original article: Nanoscopic insights into seeding mechanisms and toxicity of a-synuclein species in neurons. Proc National Academy of Sciences USA: March 18, 2016.
Scientist have identified the point at which alpha-synuclein, a protein closely linked to Parkinson’s progression, becomes toxic to brain cells. The results indicate that different types of alpha-synuclein may be harmful or helpful depending on their structure.
Why is it important?
Understanding how and why these proteins become toxic provide a clearer picture as to how and why the disease progresses, which could ultimately be used to find ways to slow or stop it.
“Tracing early events in the Parkinson’s disease process may help us develop new therapies. These types of studies are critically important.” Dr. Patrik Brundin
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Much like grains of rice, abnormal alpha-synuclein clumps together, forming the Lewy bodies found in the brains and nervous systems of people with Parkinson’s. As they stick together, the proteins form fibrils, thin wire-like filaments.
The difference between normal alpha-synuclein and abnormal alpha-synuclein lies in protein structure. Proteins start out as chains of molecules that eventually fold into a functional shape, allowing it to carry out its job. When folded incorrectly, the protein is no longer able to work properly and may cause problems.
Scientists used powerful microscopes to watch as different types of alpha-synuclein behaved to sort out a previously unknown question—at what point do these misfolded proteins become harmful to brain cells? For a long time, it was thought that fibrils had to be present to damage the cell but this work shows that the presence of a soluble form of alpha-synuclein can cause problems before fibrils form. In short, an excess of soluble alpha-synuclein is enough to cause cell damage.
Related work and trials
A recent review paper published in Nature Medicine highlights multiple research studies which demonstrates that oligomeric alpha-synuclein (soluble conformation) can cause damage to cells and are present in multiple models of Parkinson’s.
Numerous potential therapies for Parkinson’s that target alpha-synuclein are currently being researched. One drug that targets alpha-synuclein, BIIB054, is being tested in a Phase 1 multi-center trial in the US which is currently recruiting.
If you are interested in taking part in clinical trials local to you, take a look on Fox Trial Finder.
Original article: Pinotsi D, Michel CH, Buell AK, Laine RF, Mahou P, Dobson CM, Kaminski CF, Kaminski Schierle GS. March 18, 2016. Nanoscopic insights into seeding mechanisms and toxicity of a-synuclein species in neurons. Proc Natl Acad Sci U S A 113(14):3815–3819.