In Search of a Function for the N6-Methyladenosine in Epitranscriptome, Autophagy and Neurodegenerative Diseases

Abstract

Changes in epitranscriptome with N6-methyladenine (m6A) modification could be involved in the development of multiple diseases, which might be a prevalent modification of messenger RNAs (mRNAs) in eukaryotes. The m6A modification might be performed through the action of methyltransferases, demethylases, and methylation-binding proteins. Importantly, the m6A methylation may be associated with various neurological disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, aging-related diseases, and/or aging itself. In addition, the m6A methylation might functionally regulate the eukaryotic transcriptome by influencing the splicing, export, subcellular localization, translation, stability, and decay of mRNAs. Neurodegenerative diseases may possess a wide variety of phenotypes, depending on the neurons that degenerate on occasion. Interestingly, an increasing amount of evidence has indicated that m6A modification could modulate the expression of autophagy-related genes and promote autophagy in neuronal cells. Oxidative stresses such as reactive oxygen species (ROS) could stimulate the m6A RNA methylation, which may also be related to the regulation of autophagy and/or the development of neurodegenerative diseases. Both m6A modification and autophagy could also play critical roles in regulating the health condition of neurons. Therefore, a comprehensive understanding of the m6A and autophagy relationship in human diseases may benefit in developing therapeutic strategies in the future. This paper reviews advances in the understanding of the regulatory mechanisms of m6A modification in the occurrence and development of neurodegenerative diseases and/or aging, discussing the possible therapeutic procedures related to mechanisms of m6A RNA methylation and autophagy.

Potential Molecular Mechanisms of Alcohol Use Disorder with Non-Coding RNAs and Gut Microbiota for the Development of Superior Therapeutic Application

“…In the brain, the engram memory system could retain the information of a certain inflammation in the body, which may be crucially involved in the pathogenesis of immune-related diseases, in which several immunity-linked processes might be associated with certain neuronal responses to memory engrams [90]. Therefore, forgetting or emptying the bad memory of "engrams" could be promising for the prevention and/or treatment against immune-related diseases, as well as cancer, cardiac arrhythmia, and/or neurodegenerative diseases [83,91,92] (Figure 3). If that is the case with alcohol dependence, a certain adjustment of the "engram" through the alteration of the gut microbiota might be helpful as a notable treatment tactic against alcohol dependence.…”