We recently wrote about how errors in a chemical process called DNA methylation lead to wrong proteins being made in the body, increasing the risk of developing Alzheimer-related genes. The protein translation happens via messenger-RNA in cells. Another study published now in PLOS Biology identified that modifying a specific messenger RNA – m6A – could be a potential therapeutic target for Alzheimer’s.
The researchers from the Air Force Medical University, China, found that amyloid protein clearance improved when they tweaked m6A levels in mice. Amyloid beta and tau protein accumulation in the brain is a characteristic of Alzheimer’s.
Read more: Connecting the dots: Biomarkers could be key to understanding Alzheimer’s
Decoding the RNA world
RNA is a single strand of genetic material, abundantly found in cells, that carries the information code from the genes and translates them to proteins. Studies have shown that certain enzymes control the methylation of RNA, forming m6A RNA. Recent studies have shown that m6A plays a role in developing the nervous system and neurodegenerative conditions such as Alzheimer’s.
Other studies have shown that methyltransferases and demethylases are enzymes that help in attaching the chemical methyl compound to the mRNA. While the first enzyme adds the methyl group, the second removes the group at appropriate times to balance the procedure.
How neurons go missing in action
m6A has vital roles to play in generating neurons. It not only translates the protein code via mRNA but also influences stem cell generation in the bone marrow. These stem cells then form neurons.
Read more: Neurons: the building blocks of the brain
Studies found that when m6A activity was high, only proteins were made rapidly, suppressing the neuron-making process. In other words, high m6A activity reduced the production of neural stem cells.
The researchers also observed that excessive m6A influenced myeloid stem cells. These cells act on the scavenger cells or microglia in the brain. Microglia flush out the unwanted proteins in the brain.
An inside look
In the current study, the researchers deleted methyltransferases enzyme in one group of mice to reduce the m6A activity. As a result, they noticed a higher number of neural stem cells and myeloid cells in their bone marrow. When they transferred the bone marrow to mice with Alzheimer’s conditions, the microglia activity was high. The cells cleared the toxic proteins better, reducing the disease symptoms in the mice.
Depleting the methylase enzyme reduced m6A, which increased neuron formation and migration of the mature cells to their specific site in the brain, report the study authors. When they tweaked m6A in mice, they found it improved the toxic clearance of amyloid beta proteins that accumulate in Alzheimer’s condition.
“Our results suggest that m6A modifications are potential targets for treating Alzheimer’s disease,” say the authors in a statement. They are scaling their research to find out how this mechanism happens.
