Regulating PMP22 expression as a dosage sensitive neuropathy gene

Brain Res. 2020 Jan 1:1726:146491. doi: 10.1016/j.brainres.2019.146491. Epub 2019 Oct 3.

Abstract

Structural variation in the human genome has emerged as a major cause of disease as genomic data have accumulated. One of the most common structural variants associated with human disease causes the heritable neuropathy known as Charcot-Marie-Tooth (CMT) disease type 1A. This 1.4 Mb duplication causes nearly half of the CMT cases that are genetically diagnosed. The PMP22 gene is highly induced in Schwann cells during development, although its precise role in myelin formation and homeostasis is still under active investigation. The PMP22 gene can be considered as a nucleoprotein complex with enzymatic activity to produce the PMP22 transcript, and the complex is allosterically regulated by transcription factors that respond to intracellular signals and epigenomic modifications. The control of PMP22 transcript levels has been one of the major therapeutic targets of therapy development, and this review summarizes those approaches as well as efforts to characterize the regulation of the PMP22 gene.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Charcot-Marie-Tooth Disease / genetics*
  • Gene Dosage*
  • Gene Expression Regulation*
  • Humans
  • Myelin Proteins / genetics*
  • Schwann Cells / metabolism
  • Signal Transduction

Substances

  • Myelin Proteins
  • PMP22 protein, human