[The neuropathological mechanism on guanine-rich repeat expansion diseases]

Nihon Yakurigaku Zasshi. 2023;158(1):30-33. doi: 10.1254/fpj.22078.
[Article in Japanese]

Abstract

Repeat expansion diseases are caused by the aberrant repeat expansions within specific genes. RNAs derived from aberrant repeat sequences form non-canonical secondary structures, contributing to induce cell toxicity. In particular, RNA G-quadruplexes (G4RNAs) formed in guanine-rich repeat expanded RNAs trigger neurodegeneration. We have previously shown that the expanded CGG repeat-derived G4RNAs initiate aggregation of FMRpolyG, a neuropathogenic protein generated by repeat-associated non-AUG (RAN) translation in Fragile X-associated tremor/ataxia syndrome (FXTAS). In this review, we describe the neuropathological mechanism attributed to G4RNAs in guanine-rich repeat expansion diseases, including FXTAS.

Publication types

  • Review
  • English Abstract

MeSH terms

  • Ataxia / genetics
  • Ataxia / metabolism
  • Ataxia / pathology
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Mental Retardation Protein / metabolism
  • Fragile X Syndrome* / genetics
  • Fragile X Syndrome* / metabolism
  • Fragile X Syndrome* / pathology
  • Humans
  • RNA
  • Trinucleotide Repeat Expansion* / genetics

Substances

  • Fragile X Mental Retardation Protein
  • RNA

Supplementary concepts

  • Fragile X Tremor Ataxia Syndrome