Pharmacological prospects of G-quadruplexes for neurological diseases using porphyrins

Sefan Asamitsu, Yasushi Yabuki, Susumu Ikenoshita, Takahito Wada, Norifumi Shioda

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Genomic regions with guanine (G)-rich sequences make non-Watson-Crick base pairs, which result in the formation of unique nucleic acid structures called G-quadruplexes (G4s) in cells. Studies have suggested that abnormal G4s are involved in neurological diseases. For example, the formation of G4s caused by expansion of G-rich sequences is implicated in C9orf72-mediated amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), and fragile X-related tremor/ataxia syndrome (FXTAS). In addition, the disruption and/or mutation of G4 binding proteins (G4BPs), such as heterogeneous nuclear ribonucleoproteins (hnRNPs) and DNA/RNA helicases, is related to neurological diseases. For instance, mutations in a G4BP called ATRX lead to a neurodevelopmental disorder, ATR-X syndrome, which is associated with intellectual disability. We found that porphyrins are potential candidate drugs for treating ATR-X syndrome through their G4 binding ability. Importantly, intracellular porphyrins are produced from 5-aminolevulinic acid (5-ALA) in vivo. Oral administration of 5-ALA improved cognitive dysfunction in an ATR-X syndrome model mouse, and language ability in an ATR-X syndrome patient. In this review, we suggest a novel therapeutic strategy targeting G4s using porphyrins in neurological diseases.

Original languageEnglish
Pages (from-to)51-55
Number of pages5
JournalBiochemical and biophysical research communications
Issue number1
Publication statusPublished - 2020 Oct 8


  • 5- aminolevulinic acid
  • ATR-X syndrome
  • G-quadruplexes
  • Neurological diseases
  • Porphyrins

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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