- About 32 million people around the world have Alzheimer’s disease, for which there is currently no cure.
- Researchers from the Air Force Medical University in China have discovered a potential new therapeutic target for Alzheimer’s disease through the modification of mRNA.
- These mRNA modifications were able to lower cognitive symptoms of Alzheimer’s disease in a mouse model.
There is currently no cure for Alzheimer’s disease. Although there are some treatment options available, much research continues to find additional therapies.
For example, a research team at the Air Force Medical University in Xian, Shaanxi, China, has discovered a potential new therapeutic target for Alzheimer’s disease through the modification of messenger RNA (mRNA).
In a mouse model, the mRNA modifications helped improve cognitive symptoms associated with Alzheimer’s disease.
The study was recently published in the journal PLOS Biology.
RNA (ribonucleic acid) is a molecule that can be found in all living cells. The main job of RNA is to carry protein-making instructions from the DNA to the areas of the cell where proteins are made. Messenger RNA, or mRNA, is a specific type of RNA.
This movement of myeloid cells into the brain is partially regulated by a specific chemical reaction known as methylation occurring in its mRNA.
Scientists found that lowering amounts of METTL3 in a mouse model improved cognition. They also found that decreased mRNA methylation helped move more myeloid cells into the brain.
“The loss of m6A modification on mRNA of [the]
“ATAT1 is a bad guy to block [the] migration of macrophage. Inhibition of ATAT1 enhanced migration of monocyte-derived macrophages and [beta-amyloid] clearance, which led to the alleviated symptoms of Alzheimer’s disease,” Dr. Zhang explained.
When ATAT1 was lowered, researchers reported that myeloid cells were able to enter the brain, turn into macrophages, clear out amyloid-beta protein, and improve cognition in mice.
Dr. Zhang said the goal of this study was to study the function and mechanism of m6A modification of mRNA in the macrophage, especially in Alzheimer’s disease.
“We [never] realized the loss of m6A can have such a potential effect on the attenuation of Alzheimer’s disease status, but it really happens here. Our study pinpoints the potential therapeutic effect of macrophages with the loss of RNA m6A modification in the Alzheimer’s disease mouse model. If we can use a pharmacological strategy to inhibit RNA m6A modification in macrophages, it may improve the life quality of Alzheimer’s disease patients.”
– Dr. Rui Zhang
As for the next step in this research, Dr. Zhang said the team is “planning to screen and identify the m6A modification inhibitors and try to [deliver them] into the macrophage (
MNT also spoke with 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, about this study. Dr. Kesari was not involved in this research.
In his opinion, he told us, this was a very interesting potential mechanism in the treatment of Alzheimer’s disease.
“The study basically showed that […] reducing the levels of METTL3 protein increases the infiltration of immune cells from the blood into the brain to clear out the
“This is the starting point of opening up a new biology for Alzheimer’s, and validates that the immune system has a great role in
Dr. Kesari added this is the start of a variety of studies that need to be done to validate these findings and understand the mechanisms more clearly so they can be translated into humans in the future.
“Part of that really relates to potentially developing a drug that can do the same thing that the authors did in the study genetically,” he concluded.