Translation. Region: Russian Federal
Source: Peter the Great St. Petersburg Polytechnic University –
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Researchers from the Institute of Biomedical Systems and Biotechnology of Peter the Great St. Petersburg Polytechnic University (SPbPU) have proposed a new strategy to combat Alzheimer's disease. The results of their work were published in the prestigious international journal The Journal of Neuroscience.
Alzheimer's disease remains one of the most common and devastating neurodegenerative diseases in the world.data According to the World Health Organization, 57 million people worldwide suffer from dementia, with 60–70% of cases suffering from its most common form, Alzheimer's disease. As scientists note, this disease is caused by harmful substances accumulating in the brain: β-amyloid, which forms plaques, and tau protein, which curls into balls. This interferes with the normal functioning of nerve cells, disrupts the connection between them, and gradually leads to deterioration of memory and thinking. Modern therapeutic approaches are mainly associated with attempts to remove these plaques from the brain, but in practice they do not show high efficiency.
SPbPU scientists focused on another fundamental problem accompanying Alzheimer's disease — the imbalance of calcium ions inside neurons. As the authors of the study explain, calcium plays the role of a key signaling element in nerve cells. Normally, its concentration inside the cell is strictly controlled. In Alzheimer's disease, toxic β-amyloid disrupts this regulation, causing a massive and uncontrolled flow of calcium into neurons. Calcium overload leads to cell hyperactivity, disruption of neural connections and, ultimately, to their death, which is manifested by loss of memory and cognitive functions. Instead of blocking calcium channels (an approach that often leads to serious side effects), scientists proposed helping the cell cope with the problem itself. Their attention was drawn to the intracellular SERCA pump, which is responsible for pumping excess calcium into special storage facilities. The hypothesis was that enhancing the work of this pump could protect neurons from calcium stress.
In the first stage, the researchers tested six substances that could potentially activate the SERCA pump. Using cell models with a fluorescent calcium sensor, they identified the most effective compound, NDC-9009. Not only did it normalize calcium levels in neurons better than others, but it also protected them from the damaging effects of β-amyloid, preserving the integrity of dendritic spines, structures that are critical for memory formation. Having confirmed its effectiveness in cell models, the scientists moved on to testing on mice with an Alzheimer's disease model. To monitor brain function in real time, they used cutting-edge technology — miniscopeIt is a miniature microscope that is attached to the head of a freely moving rodent and allows the activity of hundreds of neurons to be recorded simultaneously, for example in the hippocampus, the brain's memory center.
Mice with Alzheimer's disease showed chaotic and excessive neuronal activity. After a course of intraperitoneal administration of NDC-9009, the activity of their neural networks normalized, becoming similar to that of healthy animals. More importantly, this restoration of brain function was accompanied by a clear improvement in memory and learning ability in behavioral tests. The analysis of data obtained from the miniscope was carried out using software we developed earlier NeuroactivityToolkit, — explained Evgeny Gerasimov, a research engineer at the Laboratory of Molecular Neurodegeneration and the Laboratory of Biomedical Image and Data Analysis at SPbPU.
These results indicate that SERCA pump modulators, and NDC-9009 in particular, offer a promising new avenue for the treatment of Alzheimer's disease. This approach targets a fundamental mechanism of cell death, calcium imbalance, and may have a more favorable safety profile than existing therapies.
The work was completed by a team of authors: Evgeny Gerasimov, Anastasia Rakovskaya, Ekaterina Pchitskaya, Olga Vlasova, Dal Russell and Ilya Bezprozvanny within the framework of project No. 075-15-2024-548 in priority areas of scientific and technological development of the Ministry of Science and Higher Education of the Russian Federation.
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