Poly-GR dipeptide repeat polymers correlate with neurodegeneration and Clinicopathological subtypes in C9ORF72-related brain disease.

ABSTRACT: Frontotemporal lobar degeneration (FTLD) is heterogeneous in clinical presentation, neuropathological characteristics and genetics. An expanded GGGGCC hexanucleotide repeat in C9ORF72 is the most common genetic cause of both FTLD and motor neuron disease (MND). Dipeptide repeat polymers (DPR) are generated through repeat-associated non-ATG translation, and they aggregate in neuronal inclusions with a distribution distinct from that of TDP-43 pathology. Recent studies from animal and cell culture models suggest that DPR might be toxic, but that toxicity may differ for specific DPR. Arginine containing DPR (poly-GR and poly-PR) have the greatest toxicity and are less frequent than other DPR (poly-GP, poly-GA). A unique feature of arginine-containing DPR is their potential for post-translatio

SUBMITTER: Sakae N 

PROVIDER: S-EPMC6054740 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature