In a mouse model, reducing the methylation of a messenger RNA may aid in the migration of macrophages to the brain and alleviate Alzheimer's disease symptoms, according to a new research.
Rui Zhang of Air Force Medical University in Xian, Shaanxi, China performed a new study on March 7th in the open access journal PLOS Biology. The findings suggest a novel strategy for treating Alzheimer's disease.
The accumulation of proteinaceous, extracellular amyloid-beta plaques in the brain is a known trigger for Alzheimer's disease, and the reduction of amyloid-beta is a major goal in the development of novel treatments.
The migration of blood-derived myeloid cells into the brain, as well as their maturation into macrophages, is a complex process controlled by many different players, and a potentially important one is the methylation of messenger RNA within myeloid cells.
The most common form of mRNA methylation, called m6A, is carried out by the enzyme METTL3, so the authors first investigated whether myeloid cells affected cognition in the Alzheimer's disease mouse model. They discovered that it did, and that treated mice performed better on various cognitive tests.
The authors investigated how decreased mRNA methylation promoted myeloid cell migration. That resulted in a loss of another protein, called ATAT1, which in turn promoted myeloid cell migration into the brain, as well as enhanced amyloid-beta clearance and improved cognition in mice.
According to the authors, m6A modifications may be beneficial for the treatment of Alzheimer's disease, while noting that much more about this pathway in Alzheimer's disease remains to be explored. Effective drug development within this pathway may require moving further downstream to avoid undesirable effects.
Huilong Yin, Zhuan Ju, Minhua Zheng, Yidi Wang, Xiaochen Ding, Xiaofang Zhang, Jiadi Li, Angang Yang, and Rui Zhang, 7 March 2023, PLOS Biology. DOI: 10.1371/journal.pbio.3002017
The National Natural Science Foundation of China gave the study $31801128 to Y.H.L., 81630069 to Y.A., 82173046 to Z.R., and 82173162 to Z.X. The funders had no role in the study design, data collection, or manuscript preparation.
