Erschienen in:
21.01.2019 | Correspondence
Antisense RNA foci are associated with nucleoli and TDP-43 mislocalization in C9orf72-ALS/FTD: a quantitative study
verfasst von:
Olubankole Aladesuyi Arogundade, Jennifer E. Stauffer, Shahram Saberi, Sandra Diaz-Garcia, Sahana Malik, Hani Basilim, Maria J. Rodriguez, Takuya Ohkubo, John Ravits
Erschienen in:
Acta Neuropathologica
|
Ausgabe 3/2019
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Excerpt
Three main mechanisms are thought to contribute to neurodegeneration in C9ORF72 amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD): toxicity from transcribed expanded repeat RNAs, toxicity from RAN-translated dipeptide repeat proteins (DPRs), and loss of C9ORF72 protein function [
4,
5,
9,
11,
12,
18]. Sense and antisense RNA foci have both been consistently observed in C9-ALS/FTD neuropathology [
1,
3,
5,
8,
9,
18] and hypothesized to cause neurodegeneration by sequestering critical RNA-binding proteins [
2,
6]. Antisense, but not sense RNA foci have been shown to correlate with mislocalization of TDP-43, a signature protein of ALS and frontal–temporal lobar degeneration (FTLD) [
1]. A unique circumferential studding of nucleoli by antisense RNA foci was observed in a case report of two C9-FTLD cases [
17] and recently re-discussed with two additional cases [
16]. Understanding the relative contributions from sense and antisense strands to pathogenesis is critical, since antisense oligonucleotides (ASOs) are expected to ameliorate toxicity whether stemming from RNAs or DPRs. …
