In a groundbreaking study, scientists at MIT’s Picower Institute for Learning and Memory have developed a molecule called “A11” that shows promise in human cell cultures and mouse models of Alzheimer’s to reduce inflammation and improve memory.
This molecule, which targets a genetic transcription factor called PU.1, could open up a new avenue to treat inflammation in Alzheimer’s disease, a major problem that’s not being adequately addressed by existing drugs.
The Science: Focusing on PU.1
The transcription factor PU.1 becomes overactive during Alzheimer’s disease in controlling inflammatory gene expression in microglia, the brain’s immune cells.
The A11 molecule mitigates this by recruiting other proteins to suppress the inflammatory genes that PU.1 activates.
Remarkably, A11 does not affect PU.1’s other essential functions, such as regulating the production of various blood cells.
Li-Huei Tsai, the study’s senior author and MIT’s Picower Professor of Neuroscience, explained that A11 “reduced inflammation in human microglia-like cells as well as in several mouse models of Alzheimer’s disease and significantly improved cognition in the mice.”
research and knowledge
Researchers validated PU.1 as a useful therapeutic target by examining gene expression in postmortem brain samples from Alzheimer’s patients and comparing them to non-Alzheimer’s controls.
They discovered that PU.1 plays an important role in altered microglial gene expression in Alzheimer’s.
After screening over 58,000 small molecules, they identified A11 as the most potent agent to safely reduce key inflammation and Alzheimer’s-related genes regulated by PU.1.
In human cell cultures, A11 potently reduced the expression of inflammatory markers and altered cell body shape changes associated with microglial inflammation.
Preclinical tests: mice and mazes
In mouse models designed to mimic various aspects of Alzheimer’s pathology, A11 reduced inflammation, neuronal death and even significantly reduced amyloid and phosphorylated tau protein levels, another hallmark of Alzheimer’s disease.
Importantly, mice treated with A11 scored significantly better on memory tests compared to untreated controls.
The Future: A Complementary Approach
While A11 still needs more extensive testing before it can be approved as a drug, it could potentially be used alone or in conjunction with existing treatments that focus on reducing amyloid beta protein.
“Given that A11 acts through a different mechanism than existing AD therapeutics, A11 may offer improved treatment options for neurodegenerative diseases,” the authors concluded.
In summary, the A11 molecule could represent a new frontier in the treatment of Alzheimer’s disease, particularly in addressing the intractable problem of inflammation, thereby opening the door to broader and more effective therapies for this devastating disease.
If you are interested in Alzheimer’s disease, please read studies showing that poor lifestyle choices can cause Alzheimer’s disease and that this new drug may help treat Alzheimer’s disease.
For more information on brain health, check out recent studies on a new early sign of Alzheimer’s disease. The results show that this brain problem can increase the risk of stroke for up to five years.
The study was published in the Journal of Experimental Medicine.
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