Axonal mRNA translation in neurological disorders

RNA Biol. 2021 Jul;18(7):936-961. doi: 10.1080/15476286.2020.1822638. Epub 2020 Sep 29.


It is increasingly recognized that local protein synthesis (LPS) contributes to fundamental aspects of axon biology, in both developing and mature neurons. Mutations in RNA-binding proteins (RBPs), as central players in LPS, and other proteins affecting RNA localization and translation are associated with a range of neurological disorders, suggesting disruption of LPS may be of pathological significance. In this review, we substantiate this hypothesis by examining the link between LPS and key axonal processes, and the implicated pathophysiological consequences of dysregulated LPS. First, we describe how the length and autonomy of axons result in an exceptional reliance on LPS. We next discuss the roles of LPS in maintaining axonal structural and functional polarity and axonal trafficking. We then consider how LPS facilitates the establishment of neuronal connectivity through regulation of axonal branching and pruning, how it mediates axonal survival into adulthood and its involvement in neuronal stress responses.

Keywords: Neurological disorders; RNA-binding protein; axon branching; axon survival; axonal trafficking; local protein synthesis; neuronal stress.

Publication types

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

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Axons / metabolism*
  • Axons / pathology
  • Gene Expression Regulation, Developmental
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / metabolism
  • Intellectual Disability / pathology
  • Mutation
  • Nerve Net / growth & development
  • Nerve Net / metabolism
  • Nerve Net / pathology
  • Nerve Tissue Proteins / classification
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity / genetics
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Protein Biosynthesis*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism


  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins