pte20200702013 Medicine / Wellness, Research / Development
Knowledge of protein damage will help future drug development
Vesicle: Alpha synuclein damage (Photo: Fredrik Höök)
Gothenburg (pte013 / Jul 2, 2020 / 11:30 am) – Patients with Parkinson’s have evidence of clumps of alpha-synuclein in the brain, also known as “Parkinson’s protein”. They destroy the cell membranes and eventually lead to cell death. Researchers at Chalmers University of Technology http://chalmers.se have now developed a process that shows how even small amounts of alpha-synuclein can cause damage.
Parkinson’s is an incurable disease in which the neurons gradually collapse and brain functions are disrupted. Symptoms may include involuntary tremors in the body. To develop drugs that slow or stop the disease, researchers are trying to understand the molecular mechanisms of the role of alpha-synuclein in the degeneration of neurons.
Parkinson’s protein doesn’t always harm
The current study focuses on two different types of membrane-like vesicles. These are capsules made of lipids that can be used to imitate the membrane in the cells. One of the vesicles consists of lipids that are frequently detected in the synaptic vesicles, the other contains lipids that are connected to the mitochondrial membranes.
According to research director Pernilla Wittung-Stafshede, it was possible to develop a method that is sensitive enough to observe how alpha-synuclein interacts with different model vesicles. The researchers were able to demonstrate that the Parkinson’s protein binds to both types of vesicles. However, structural changes only occur in the mitochondrial-like vesicles. These deformed asymmetrically and released their contents.
Without fluorescent markers
The new process makes it possible to research tiny amounts of biological molecules without fluorescent markers. This is a great advantage when observing natural reactions. Markers often influenced the reactions to be examined. This is especially true when working with small proteins such as alpha-synuclein. According to Wittung-Stafshede, the chemical differences between the two lipids are very small.
Nevertheless, it was possible to determine dramatic differences in the effects of alpha-synuclein on the various vesicles. “We assume that lipid chemistry is not the only determining factor, but that there are other macroscopic differences between the two membranes. Examples of this are the dynamics and the interaction between the lipids. Nobody has researched exactly what with the membrane even happens when alpha synuclein binds, and certainly not in these low concentrations, “says Wittung-Stafshede. The research results were published in “PNAS”.