THE ESSENTIAL
- CUNY ASRC researchers have discovered a mechanism linking cellular stress to the progression of Alzheimer’s disease.
- They identified a phenotype of microglia, the brain’s immune cells, activated by an integrated stress response (ISR). This activation pushes microglia to produce toxic lipids, damaging neurons and brain cells.
- Inhibition of the ISR or the production of these lipids made it possible to prevent symptoms in mice, opening a promising therapeutic avenue.
What if the fight against Alzheimer’s disease involved our own immune cells? A new study from the Advanced Science Research Center (CUNY ASRC), in the United States, reveals how cellular stress in the brain activates a mechanism that triggers neurodegeneration. Detailed in the review Neuronthis process, which involves microglia (the main immune cells of the brain), could open up new therapeutic avenues.
A discovery at the heart of cellular stress
Microglia play a fundamental role in brain health. On the one hand, they protect neurons from external attacks; on the other, they can worsen the damage by releasing toxic substances. It is this duality that has attracted the attention of researchers. “We sought to understand which microglia are harmful in Alzheimer’s disease and how to target them therapeutically”they explain in a press release. The team identified a new type of neurodegenerative microglia, activated by a signaling pathway linked to cellular stress, called integrated stress response (ISR).
This ISR pathway induces microglia to produce toxic lipids. These substances damage neurons and oligodendrocyte precursor cells, which are essential for brain function. However, by blocking this stress response or lipid synthesis, researchers have succeeded in reversing Alzheimer’s symptoms in mouse models.
The study notably identified a specific subtype of microglia, called “dark microglia”, twice as present in the post-mortem brain tissue of Alzheimer’s patients than in that of healthy elderly individuals. These cells appear strongly associated with cellular stress and loss of synapses, one of the key markers of the disease.
Towards new therapeutic solutions?
“These findings highlight a critical link between cellular stress and the neurotoxic effects of microglia in Alzheimer’s,” say the scientists. Their results open encouraging perspectives for the treatment of neurodegenerative disease. By targeting the mechanisms that produce toxic lipids or preventing the activation of harmful microglia, it would theoretically be possible to slow down or even reverse the progression of the disease.
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