BrainStorm Live Episode 7: What Is The Molecular Basis Of Parkinson’s?
Amprion’s CEO Dr. Russ Lebovitz discusses the molecular basis of Synuclein, a type of Prion (aka misfolded-protein) underlying Parkinson’s disease and compares this with the molecular footprint and Prion structures associated with Alzheimer’s.
Synuclein is the Molecular Basis for Parkinson’s
Well actually it’s a very parallel situation where Alzheimer’s seems to be a disease of misfolding of Tau and Abeta; Parkinson’s is a disease of a very similar misfolding of a third protein called Synuclein. Again, Synuclein is a normal protein in the brain which is necessary for normal brain function. But in certain cases the normal form of Synuclein can misfold into two different shapes and they have two different structures that are formed. So if it misfolds in one shape you get very large aggregates which appear in the brains of patients with Parkinson’s disease. And these are called Lewy Bodies.
This is a hallmark under the microscope of the disease. But the Lewy Bodies, like plaque and tangle for Alzheimer’s are very large and insoluble and can’t spread throughout the brain. So they are a sign of the disease but probably less likely to be a direct cause of the disease. However, Synuclein clearly can misfold into a slightly different shape which forms small aggregates and the difference here, this might be hundreds, thousands, or even millions of Synuclein molecules in a large clump.
The soluble aggregates are somewhere generally between 10 and 25, maybe as many as 100. But these remain soluble, so they can spread from cell to cell. They can spread throughout the brain and they can cause disease that is much more widespread than the very very large Lewy Bodies in clumps. So again, for Abeta, Tau and Synuclein, the disease at a molecular level appears to be caused by misfolding of normal proteins in a way that can spread throughout the brain. Amprion has technology that can uniquely detect this small aggregate, this smaller misfolded form, that seems to be the actual cause of the disease and its progression.
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