Scientists watch protein drilling holes in Parkinson’s in brain cells

Parkinson’s disease often begins skillfully. A slight tremor in the hand. A little hardness. But over time, brain cells begin to die, and symptoms increase. The reason has long been a mystery – but scientists may now be a step closer to interpretation.

In the center of attention there is protein α-synuclein, which plays a role in communication from the cell to the cell in the healthy brain. However, in Parkinson, it begins to act abnormally and clog in toxic structures.

To date, most research has focused on large groups known as fiber, which are visible in the brain tissue of patients with Parkinson’s. But a new study focuses on smaller, less understanding and more toxic structures: α-synuclein. According to researchers, these are those that dig microscopic holes in the membranes of neurons.

The study was recently published in the prestigious magazine ACS NanoPublished by the American Chemical Society.

Small circuit doors in cells

“We are the first to directly notice how this few pores – and how the pores act,” says Miti Galsgard Malley, post -PhD researcher at Arahus University and Harvard University.

The process is revealed in three steps. First, the lack of a few attach to the membrane, especially in the curved areas. Then they are partially studied in the membrane. Finally, they form a pore that allows molecules to pass through and may disrupt the internal balance of the cell.

But these are not fixed holes. The pores are constantly opened and closed like small renewable doors.

“This dynamic behavior may help explain the reason why the cells do not die immediately,” says Bo Volf Brächner, a doctorate student and the first author of the study. “If the pores remain open, the cells are likely to collapse very quickly. But since they are open and close, the special cell pumps may be able to compensate temporarily.”

The molecular film in a slow movement

This is the first time that these pores dynamics have been observed in the actual time. It has become possible through the newly developed single bacilli analysis platform that allows researchers to follow interactions between individual proteins and individual vesicles.

Al -Huweisat is small artificial bubbles that mimic cell membranes and serve as simplified models of real cells.

“It is like watching a molecular movie in a slow movement,” explains Mette Galsgaard Malle. “We can only see what is happening – we can also test how different molecules affect the process. This makes the platform a valuable tool for drug examination.”

A long path to treatment

In fact, the team has already tested nanoparticles – small antibody fragments – was developed to link this few specifically. It shows the promise as very selective diagnostic tools. However, as a treatment, there is still a way to go.

“The nanoparticles have not prevented the formation of pores,” says Bo Volf Brächner. “But they may still help discover the few in the early stages of the disease. This is very important, as Parkinson’s is usually diagnosed only after significant nervous damage.”

The study also shows that the pores are not randomly formed. It tends to appear in specific types of membranes – especially those that resemble mitochondria, cell power factories. This can indicate that the damage begins there.

One step every time

However, the researchers emphasize that the study was conducted in typical systems – not in living cells. The next step is to repeat the results in biological tissues, where more complex factors are turned on.

“We have created a clean experimental preparation where we can measure one thing at one time. This is the power of this platform,” says Mette Galsgaard Malle. “But now we need to take the next step and investigate what is happening in the most complex biological systems.”