Unconventional features of C9ORF72 expanded repeat in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

摘要: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are devastating neurodegenerative diseases that form two ends of a complex disease spectrum. Aggregation RNA binding proteins is one the hallmark pathologic features ALS FTDL suggests perturbance metabolism in their etiology. Recent identification disease-associated expansions intronic hexanucleotide repeat GGGGCC C9ORF72 gene further substantiates case for involvement. The expanded repeat, which has turned out to be single most common genetic cause FTLD, may enable formation DNA structures, changes transcription, processing toxic foci, sequester inactivate proteins. Additionally, transcribed can undergo repeat-associated non-ATG-initiated translation resulting accumulation series dipeptide Understanding basis proposed mechanisms shared pathways, as well interactions with known key such TAR DNA-binding protein (TDP-43) needed clarify pathology and/or make possible steps toward therapy development.