- New research highlights the potential of anti-inflammatory drugs, specifically p38 inhibitors, as a treatment for Alzheimer’s disease.
- Scientists at the University of Kentucky’s Sanders-Brown Center on Aging focused on the protein p38, which is being studied by various labs for its role in neuroinflammatory dysfunction.
- By genetically suppressing p38 production in microglia, immune cells in the brain, the researchers observed a decrease in the number of microglia near amyloid plaques, a hallmark of Alzheimer’s.
- These findings suggest that early inhibition of p38 could impact the interaction between brain immune cells and Alzheimer’s disease pathology.
To understand how blocking the production of p38 protein could help with Alzheimer’s disease, the researchers conducted tests on an early-stage mouse model of Alzheimer’s disease.
In this new study, published in
The researchers wanted to see if this intervention could change the way amyloid plaques, which are a key feature of Alzheimer’s, develop in the brain.
The
Scientists are studying this protein as a potential target for developing drugs to treat Alzheimer’s disease and other conditions where there are problems with inflammation in the brain.
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The drugs that inhibit p38-alpha might be helpful because they can regulate the way certain brain cells called microglia respond to inflammation.
These microglia are involved in the inflammatory processes that contribute to the development of Alzheimer’s disease.
Although the plaques themselves were not directly influenced by blocking p38, the researchers noticed that the number of microglia cells near these plaques decreased.
This suggests that when p38 production is suppressed in microglia, it may affect how these cells interact with the aspects of Alzheimer’s disease pathology, including amyloid plaques.
Certain types of anti-inflammatory drugs, such as p38 inhibitors, are being developed as potential treatments for Alzheimer’s disease. These drugs have shown promising results in
However, there are still questions to be answered, for example, when exactly during the progression of Alzheimer’s disease these p38 inhibitors should be administered to be most effective.
It would also be important to determine whether long-term suppression of p38 could have any negative effects on the body, although early results suggest that it does not seem to cause any noticeable harmful effects.
The findings from the research suggest that early use of p38 inhibitors may be able to change how immune cells in the brain interact with Alzheimer’s disease-related changes.
Dr. Santosh Kesari, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, and regional medical director for the Research Clinical Institute of Providence Southern California, not involved in this research, told Medical News Today that “inflammation is thought to play a role in neurodegenerative disorders and this article tested whether p38 protein in brain microglia is involved in Alzheimer’s pathology in a mouse model.”
“Microglia p38 modulates in immune responses in brain pathologies. The authors knocked out p38 in microglial specifically to see how it affected behavioral and pathological changes in [an] amyloid Alzheimer’s model,” Dr. Kesari explained.
“Interestingly, the p38 loss in microglia did not alter behavioral outcomes, information levels, or amyloid plaque levels despite increase in levels of [beta-amyloid-42] and distribution of microglial around plaques.”
– Santosh Kesari
Dr. Raymond J. Tesi, CEO and chief medical officer at INmune Bio, also not involved in the study, also reviewed the findings for MNT, saying that his “conclusion is that blocking the p38a pathway in this animal model did not have any effect on cognitive function.”
Dr. Kesari pointed out that “this is an early study exploring the role of microglial p38 in amyloid formation and dementia.”
“While p38 loss shows subtle effects in brain pathology, more studies will need to be done to see how significant this protein is in Alzheimer’s related pathology and if it represents a good target for future drug development to treat Alzheimer’s and other related dementias,” Dr. Kesari explained.
Dr. Tesi went further, saying that “INmune Bio does not believe amyloid plaques are a therapeutic drug target, but a biomarker of disease.”
“Put in simple English, we are not surprised that cognition was not altered by plaque burden because it is not part of the pathophysiology of the disease.”
“An implication for humans may be that amyloid plaques are not related to cognitive function. This is consistent with the observation that many people die with amyloid plaques in their brains and normal cognitive function.”
– Dr. Raymond J. Tesi
Ultimately, more research is needed.
