Emerging Role of microRNAs in Dementia

J Mol Biol. 2019 Apr 19;431(9):1743-1762. doi: 10.1016/j.jmb.2019.01.046. Epub 2019 Feb 7.

Abstract

MicroRNAs are small non-coding RNAs regulating mRNA translation. They play a crucial role in regulating homeostasis in neurons, especially in regulating local and stimulation dependent protein synthesis. Since activity-mediated protein synthesis in neurons is critical for memory and cognition, microRNAs have become key players in modulating these processes. Dementia is a broad term used for symptoms involving decline of memory and cognition. Several studies have implicated the dysregulation of microRNAs in many brain diseases like neurodegenerative diseases, neurodevelopmental disorders, brain injuries and dementia. In this review, we give an overview of microRNA-mediated regulation of proteins and cellular processes affected in dementia pathology, hence illustrating the importance of microRNAs in normal functioning. We also focus on a relatively less explored area in dementia pathology-the importance of activity-mediated protein synthesis at the synapse and the role of microRNAs in modulating this. Overall, this review will be helpful in looking at the significance of microRNAs in dementia from the perspective of defective regulation of protein synthesis and synaptic dysfunction.

Keywords: Alzheimer's disease; fronto-temporal dementia; microRNA processing; synaptic dysfunction; translation regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADAM10 Protein / genetics
  • ADAM10 Protein / metabolism
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Endopeptidases / metabolism
  • Autophagy / genetics
  • Dementia / genetics*
  • Dementia / metabolism
  • Dementia / pathology
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mitophagy / genetics
  • Neurons / metabolism*
  • Neurons / pathology
  • Protein Biosynthesis
  • Synapses / metabolism*
  • Synapses / pathology
  • Synaptic Transmission
  • tau Proteins / genetics*
  • tau Proteins / metabolism

Substances

  • APP protein, human
  • Amyloid beta-Protein Precursor
  • MAPT protein, human
  • Membrane Proteins
  • MicroRNAs
  • tau Proteins
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • ADAM10 Protein
  • ADAM10 protein, human