Repeat associated non-atg translation and its regulation in C9orf72-associated amyotrophic lateral sclerosis/frontotemporal dementia model fly

Abstract

Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are intractable neurological diseases with overlapping genetic and neuropathological features. Recently, an abnormal expansion of GGGGCC (G4C2) repeat in the first intron of C9orf72 gene has been found to be the genetic mutation for ALS/FTD. The expanded repeat RNA transcribed from mutated gene is translated into dipeptide repeat (DPR) proteins by unconventional translation, the so-called repeat associated non-ATG (RAN) translation. Although the toxicity associated with DPR proteins though to be involved in the pathogenesis of C9orf72-associated ALS/FTD (C9-ALS/FTD), little is known about mechanism regulating RAN translation.