Thesis / Dissertation

In vitro investigation of dipeptide repeat proteins in C9ORF72-associated motor neuron disease and frontotemporal dementia

Mona Radwan Ahmed Elsayed, Daniel Hatters (ed.)

Published : 2020

Abstract

Mutations that expand a hexanucleotide (GGGGCC) tandem repeat sequence (HTRS) in intron-1 of the C9ORF72 gene is the major cause of familial motor neuron disease MND and frontotemporal dementia (FTD). The expanded HTRSs trigger abnormal bi-directional transcription, which generates both sense and antisense RNA transcripts that form foci. The subsequent translation of all reading frames of HTRSs generates five types of dipeptide repeat proteins (DRPs) via Repeat-Associated Non-ATG (RAN) translation. The sense (G4C2) RNA encodes poly-glycine-alanine (poly-GA), poly-glycine-proline (poly-GP), and poly-glycine-arginine (poly-GR), while the antisense (C4G2) RNA generates poly-GP, poly-proline-arg..

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