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01-03-2019 | Amyotrophic Lateral Sclerosis | Correspondence

Antisense RNA foci are associated with nucleoli and TDP-43 mislocalization in C9orf72-ALS/FTD: a quantitative study

Authors: Olubankole Aladesuyi Arogundade, Jennifer E. Stauffer, Shahram Saberi, Sandra Diaz-Garcia, Sahana Malik, Hani Basilim, Maria J. Rodriguez, Takuya Ohkubo, John Ravits

Published in: Acta Neuropathologica | Issue 3/2019

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. …

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Title: Antisense RNA foci are associated with nucleoli and TDP-43 mislocalization in C9orf72-ALS/FTD: a quantitative study
Authors: Olubankole Aladesuyi Arogundade
Jennifer E. Stauffer
Shahram Saberi
Sandra Diaz-Garcia
Sahana Malik
Hani Basilim
Maria J. Rodriguez
Takuya Ohkubo
John Ravits
Publication date: 01-03-2019
Publisher: Springer Berlin Heidelberg
Keywords: Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Frontotemporal Dementia
Published in: Acta Neuropathologica / Issue 3/2019
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-018-01955-0

At a glance: The STEP trials

Springer Medicine

Antisense RNA foci are associated with nucleoli and TDP-43 mislocalization in C9orf72-ALS/FTD: a quantitative study

Excerpt

At a glance: The STEP trials

Springer Medicine

Excerpt

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