Scientists studying Alzheimer’s disease have made a major breakthrough by identifying a vital cellular mechanism behind the most common cause of dementia.
The City University of New York (CUNY) research represents a promising target for drug therapies that could slow or even reverse the development of the disease.
The study, published in the journal Neuron, highlights microglia – the brain’s primary immune cells – and their critical link to cellular stress in the brain – both the protective and harmful responses associated with Alzheimer’s disease.
Microglia, often considered the first responders of the brain, are now recognized as an important causal cell type in Alzheimer’s pathology. However, these cells play a double-edged role: some protect brain health, while others worsen neurodegeneration.
“We set out to figure out what microglia are harmful in Alzheimer’s disease and how can we target them therapeutically,” said Pinar Ayata, principal investigator of the study and professor in the CUNY Neuroscience Initiative within of its advanced scientific research center.
His team identified a “new neurodegenerative phenotype of microglia” in Alzheimer’s disease, characterized by a stress-related signaling pathway.
Activation of this stress pathway, known as the integrated stress response (ISR), induces microglia to produce and release toxic lipids. These lipids damage neurons and oligodendrocyte progenitor cells, two types of cells essential to brain function and most affected in Alzheimer’s disease.
Blocking this stress response or lipid synthesis pathway reversed Alzheimer’s disease symptoms in preclinical models.
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Using electron microscopy, the research team identified an accumulation of “dark microglia,” a subset of microglia associated with cellular stress and neurodegeneration, in postmortem brain tissue from patients with AD. ‘Alzheimer’s.
The cells were present at levels twice those seen in healthy people.
“These results reveal a critical link between cellular stress and the neurotoxic effects of microglia in Alzheimer’s disease,” declared the co-leader of the study author Anna Flury.
Ms. Flury, a member of Professor Ayata’s laboratory and a Ph.D. According to one student, “targeting this pathway could open new avenues of treatment, either by stopping the production of toxic lipids or by preventing the activation of harmful microglial phenotypes. »
The team’s study highlights the potential for drug development targeting specific microglial populations or their stress-induced mechanisms.
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“Such treatments could significantly slow or even reverse the progression of Alzheimer’s disease, offering hope to millions of patients and their families,” concluded co-senior author Leen Aljayousi, a member of the laboratory of the Professor Ayata.
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