Scientists may have uncovered a new mechanism for treating Alzheimer's disease, offering hope to millions of patients worldwide.
The discovery involves the activation of the brain's cellular clean-up crew, resulting in improvements in memory and cognitive function in mouse models.
Alzheimer's affects roughly 5.8 million Americans, according to the Centers for Disease Control and Prevention. The progressive disease is the most common form of dementia and is associated with memory loss and cognitive decline in regions of the brain involved in thought, memory and language.
Today, there is no known cure for Alzheimer's, although scientists believe that it is caused by the abnormal buildup of proteins in and around the brain cells. In the past, scientists observed that special immune cells in the brain called astrocytes became activated in response to these protein clumps. But the mechanisms by which the astrocytes are able to remove the protein clumps are not well understood.
Now, scientists from the Korea Institute of Science and Technology, along with the Institute for Basic Science and Boston University, have shown that the presence of these protein clumps activates cellular recycling pathways in these cells, turning them into protein clearing machines.
The transformation appears to be mediated by temporarily switching on specific genes involved in this recycling process. Therefore, the research team hypothesized that if we were able to artificially induce this transformation, we might be able to facilitate the removal of these protein clumps in the brains of Alzheimer's patients.
To explore this further, the team used a group of genetically engineered mice that have been designed to model Alzheimer's disease. They found that, by activating these recycling genes, the damaged neurons in the mice's brains began to recover, resulting in improved memory and cognitive functions.
Meanwhile, inhibiting these genes showed a significant worsening of Alzheimer's symptoms, including an increased build-up of these protein clumps and subsequent neuronal damage.
More work needs to be done to confirm these results in humans, but the study offers new insights into the protective mechanisms used by our brains to ward off neurodegenerative disorders, and proposes a potential new therapeutic target for future drug development.
"We hope this study will advance our understanding of cellular mechanisms related to autophagy [cellular recycling] and contribute to future research on waste removal by astrocytes and health maintenance of the brain," co-authors Hoon Ryu and Suhyun Kim said in a statement.
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References
Kim, S., Chun, H., Kim, Y. et al. Astrocytic autophagy plasticity modulates Aβ clearance and cognitive function in Alzheimer's disease. Mol Neurodegeneration, (2024). https://doi.org/10.1186/s13024-024-00740-w
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