en.Wedoany.com Reported - A research team from the Institute of Neuroscience at the Spanish National Research Council - Miguel Hernández University (CSIC-UMH) published a study in the journal *Cell Death & Disease*, finding that a compound called OLE helps microglial cells surround and encapsulate β-amyloid plaques, thereby reducing their size and toxicity. In animal models, this treatment also improved cognitive performance in memory tests.
Alzheimer's disease is characterized by the accumulation of β-amyloid plaques and the progressive degeneration of microglial cells. Microglial cells are immune cells responsible for clearing these toxic deposits from the brain. As the disease progresses, these cells lose some of their protective capacity and contribute to neuronal damage. In this study, researchers found that OLE, a molecule derived from the PM20D1 gene, helps restore microglial cells to a more protective state: the cells move toward the plaques and encapsulate them, forming a barrier around the deposits that limits their interaction with neurons and reduces their toxic effects on brain tissue.
"One of the most important findings is that we have identified a molecule capable of restoring the protective function of microglial cells," explained Sánchez Mut. "In Alzheimer's disease, these cells become progressively impaired. Our results indicate that this process is reversible, pointing to new therapeutic and research directions for combating the disease," added the researcher, who leads the Functional Epigenomics of Aging and Alzheimer's Disease Laboratory at the CSIC-UMH Institute of Neuroscience (IN CSIC-UMH).
To study the effects of OLE, the team combined different experimental models. First, they used *Caenorhabditis elegans* genetically modified to produce β-amyloid, allowing researchers to rapidly assess its toxicity. In this model, OLE treatment reduced the accumulation of protein aggregates and improved the worms' motility, indicating a protective effect against disease-related damage.
Subsequently, the team administered the compound to a mouse model of Alzheimer's disease for three consecutive months to analyze its effects on the brain and memory. After treatment, the animals showed improved performance in memory tests and a reduction in β-amyloid plaques associated with the disease.
To understand the mechanism of OLE action in the brain, the team analyzed the activity of thousands of individual cells. The results showed that microglial cells were the cell type most sensitive to the treatment. After administering the compound, these cells activated mechanisms involved in β-amyloid clearance and regained their ability to move toward and encapsulate plaques. "Single-cell analysis allowed us to determine that microglial cells are the ones that respond most strongly to the treatment," said Victoria Pozzi, first author of the study. "From this, we observed that the compound helps these cells move toward β-amyloid plaques and better control the damage associated with the disease," she added.
Furthermore, the team confirmed in cell culture that microglial cells treated with OLE showed an enhanced ability to move toward β-amyloid deposits and promote their clearance. Similarly, in neuronal cultures exposed to conditions mimicking Alzheimer's disease stress, the treatment increased cell survival, indicating that it also exerts a direct protective effect on neurons.
The results of this study are protected by two European patents, one of which is held by the Spanish National Research Council (CSIC). According to the authors, this progress enhances the translational potential of the research and its possible future development in the therapeutic field.
The completion of this study was made possible by funding from: the Swiss Dementia Research – Synapsis Foundation, the Pascual Maragall Foundation's Pascual Maragall Researchers Programme (PMRP), the Spanish Ministry of Science, Innovation and Universities, the Severo Ochoa Centre of Excellence Programme of the National Research Agency (AEI), the Prometeo Programme of the Valencian Regional Government, the European Regional Development Fund (ERDF), and the CSIC Interdisciplinary Thematic Platform PTI+ NEURO-AGING. It also received support from the Swiss National Science Foundation, the École Polytechnique Fédérale de Lausanne (EPFL), the European Research Council (ERC), the National Research Foundation of Korea (NRF), and the European Social Fund (ESF+).
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