Complex path promotes immune cell migration and clearance of toxic protein. Reducing the methylation of a key messenger RNA can promote migration of macrophages into the brain and ameliorate symptoms of Alzheimer’s disease in a mouse model, according to a new study published on March 7th in the ope
A study published in PLOS Biology suggests that reducing methylation of a messenger RNA can help in the migration of macrophages to the brain and alleviate Alzheimer’s disease symptoms in a mouse model. This study highlights a potential pathway for immune cells to enter the brain and could provide a new target for Alzheimer’s treatment.
One potential pathway for getting rid of amyloid-beta is the migration of blood-derived myeloid cells into the brain, and their maturation into macrophages, which, along with resident microglia, can consume amyloid-beta. That migration is a complex phenomenon controlled by multiple interacting players, but a potentially important one is the methylation of messenger RNA within the myeloid cells.
How did decreased mRNA methylation promote myeloid cell migration? The authors elucidated a complex mechanism. Through analysis of mRNA expression patterns and other techniques, they showed that depletion of METTL3 reduced the activity of a key m6A reader protein, which recognizes m6A-modified mRNAs and promotes their translation into protein. That led to a decline in another protein, and that inhibited the production of yet another protein, called ATAT1.
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