In a groundbreaking study, scientists at The Picower Institute for Learning and Memory at MIT have developed a molecule named “A11,” which shows promise in reducing inflammation and improving memory in human cell cultures and Alzheimer’s mouse models.
Targeting a genetic transcription factor called PU.1, this molecule could provide a new avenue for treating inflammation in Alzheimer’s disease, a major issue that existing medications have not adequately addressed.
The Science: Zeroing In On PU.1
The PU.1 transcription factor becomes overly active in directing inflammatory gene expression in the microglia, the immune cells of the brain, during Alzheimer’s.
The A11 molecule mitigates this by recruiting other proteins to suppress the inflammatory genes that PU.1 activates.
Remarkably, A11 does not impact PU.1’s other essential roles, such as regulating the production of a variety of blood cells.
Li-Huei Tsai, the senior author of the study and Picower Professor of Neuroscience at MIT, stated that A11 “reduces inflammation in human microglia-like cells as well as in multiple mouse models of Alzheimer’s disease and significantly improves cognition in the mice.”
Research and Findings
The researchers validated PU.1 as a meaningful therapeutic target by examining gene expression in post-mortem brain samples from Alzheimer’s patients and comparing it to non-Alzheimer’s controls.
They discovered that PU.1 plays a significant role in the altered microglial gene expression seen in Alzheimer’s.
After screening over 58,000 small molecules, they identified A11 as the most potent in safely reducing key inflammation and Alzheimer’s related genes regulated by PU.1.
In human cell cultures, A11 effectively reduced the expression of inflammatory markers and altered the cell body shape changes associated with microglia 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, A11-treated mice performed significantly better in memory tests compared to untreated controls.
The Future: A Complementary Approach
While A11 still needs more extensive testing before it can become an approved medication, it could potentially be used alone or in conjunction with existing treatments that focus on reducing amyloid-beta protein.
“Given that A11 acts via a distinct mechanism from existing AD therapeutics, A11 could provide improved treatment options for neurodegenerative diseases,” the authors concluded.
In summary, the A11 molecule may represent a new frontier in Alzheimer’s disease treatment, particularly in managing the intractable problem of inflammation, thereby opening the door to more comprehensive and effective therapies for this devastating disease.
If you care about Alzheimer’s disease, please read studies that bad lifestyle habits can cause Alzheimer’s disease, and this new drug may help treat Alzheimer’s disease.
For more information about brain health, please see recent studies about a new early sign of Alzheimer’s disease, and results showing this brain problem can increase risk of stroke for up to five years.
The study was published in the Journal of Experimental Medicine.
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