Alpha-synuclein cause damage to mitochondria in patients with Parkinson’s disease. These researchers wanted to see if they could see the membrane changes fostered by the alpha-synuclein. The examination of such could provide more insight in regard to the process of the disease.
They found that the alpha-synuclein impacts different membranes differently. These differences are based on the composition of the cells.
By understanding how the clumps of alpha-synuclein called amyloids disrupt membranes, they can further delve into how to stop this disruption. In other words, it could help them to find a way to stop progression of Parkinson’s disease.
This study, conducted by Swedish scientists at Chalmers University of Technology, was published in PNAS.
The Study
This study used microscopy techniques in order to investigate how the amyloids are able to disrupt cell membranes in different ways.
Two vesicles were created. The first mimicked mitochondria and the second mimicked synaptic vesicles which store neurotransmitters. Then, both of these vesicles were exposed to alpha-synuclein. The researchers monitored and documented what happened following exposure.
They found that the amyloids bound to the mitochondria and destroyed it. The amyloids made the mitochondria less rigid as well as more porous, ultimately leading to vesicle collapse. The destruction was possible because of how deep the alpha-synuclein was able to insert itself into the membrane. Before this study, researchers thought it simply laid on the surface of the membrane. On the contrary, while the amyloids still attached to the synaptic vesicles, it did not destroy them.
Why does the alpha-synuclein bind more deeply to the mitochondria membrane? The membrane has a low lipid density, contains irregularities, and has a high curvature.
Also noteworthy was the fact that it only required a small amount of alpha-synuclein molecules to foster significant structural changes.
Looking Forward
The technique used by these researchers was novel. It allowed them to study just a few molecules without needing fluorescent markers. These markers can affect the reactions that the researchers are trying to examine, so not utilizing these makes for a more reliable study.
Moving forward, the researchers plan to use this technique again with even stronger membrane replicates. They also plan to perform additional quantitative studies to document exactly how damage to the membranes occur. They want to track each individual protein to see how small variations in the properties of each foster different responses.
You can read more about this study here.
