AUTHOR=Robinson Hayley , Ali Sk Imran , Diaz-Hernandez Martha Elena , Lopez-Gonzalez Rodrigo 

TITLE=Telomere Attrition in Induced Pluripotent Stem Cell-Derived Neurons From ALS/FTD-Related C9ORF72 Repeat Expansion Carriers

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.874323

DOI=10.3389/fcell.2022.874323

ISSN=2296-634X

ABSTRACT=<p>The GGGGCC (G4C2) repeat expansion in <italic>C9ORF72</italic> is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dysregulated DNA damage response and the generation of reactive oxygen species (ROS) have been postulated as major drivers of toxicity in <italic>C9ORF72</italic> pathogenesis. Telomeres are tandem-repeated nucleotide sequences that are located at the end of chromosomes and protect them from degradation. Interestingly, it has been established that telomeres are sensitive to ROS. Here, we analyzed telomere length in neurons and neural progenitor cells from several induced pluripotent stem cell (iPSC) lines from control subjects and <italic>C9ORF72</italic> repeat expansion carriers. We found an age-dependent decrease in telomere length in two-month-old iPSC-derived motor neurons from <italic>C9ORF72</italic> carriers as compared to control subjects and a dysregulation in the protein levels of shelterin complex members TRF2 and POT1.</p>