Researchers at the Perelman School of Medicine at the University of Pennsylvania have made a significant breakthrough in Alzheimer’s disease research.
Their study, published in Aging Biology, highlights the potential of a molecule called 4-phenylbutyrate (PBA) to reverse key signs of Alzheimer’s disease, including memory loss, in mice.
Alzheimer’s disease affects millions of people around the world, with numbers expected to rise sharply in the coming years.
One of the main features of this disease is the buildup of protein aggregates in the brain, disrupting the normal functioning of brain cells. This condition leads to memory impairment and other cognitive difficulties associated with Alzheimer’s.
PBA, a fatty-acid molecule, is known to act as a “chemical chaperone.” This means it helps in maintaining the proper formation of proteins in the body.
The researchers found that when they gave injections of PBA to mice that were used as models for Alzheimer’s disease, it significantly improved the health of their brain cells.
The treatment restored the normal process of protein regulation in their brains, known as proteostasis, and greatly improved the mice’s performance in memory tests.
The exciting part of the study is that PBA was effective even when given later in the course of the disease. This suggests that it could be a promising treatment option for patients who are already showing symptoms of Alzheimer’s.
The mice used in the study, known as APPNL-G-F mice, show many similarities to humans with Alzheimer’s. They accumulate abnormal protein aggregates in their brains, lose connections between brain cells, and have severe memory impairments.
The study’s lead researcher, Dr. Nirinjini Naidoo, explained that improving the health of neurons (brain cells) can help delay or reduce the progression of the disease. By reducing the damage caused by the buildup of faulty proteins, PBA could help restore some brain functions that were previously lost.
In their experiments, the team initially treated the mice early in their life and observed that PBA helped restore normal protein regulation in areas of the brain crucial for memory.
Remarkably, the treatment also restored the mice’s ability to recognize changes in their environment, a skill they had lost due to the disease.
The team then discovered that similar benefits, including the reversal of memory deficits, were achieved even when they started treating the mice in middle age.
This finding is crucial because it suggests that PBA could be effective even after the onset of Alzheimer’s symptoms.
Interestingly, PBA treatment reduced the formation of amyloid beta plaques, which are the most prominent protein aggregates found in Alzheimer’s disease.
In mice treated later in life, the researchers noted not only a reduction in the process that forms these plaques but also a decrease in the number of plaques themselves.
PBA has the added advantage of being able to move easily from the bloodstream into the brain.
It’s also already approved by the Food and Drug Administration for treating a different metabolic disorder, which could potentially speed up the process of making it available for Alzheimer’s patients.
This study brings new hope in the fight against Alzheimer’s disease. It suggests that with PBA, there might be a way to not only halt the progression of the disease but also reverse some of its most debilitating effects, like memory loss.
While more research is needed, particularly in human trials, this represents a significant step forward in the search for effective treatments for this challenging disease.
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The research findings can be found in Aging Biology.
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