Literature DB >> 32375063

Chimeric Peptide Species Contribute to Divergent Dipeptide Repeat Pathology in c9ALS/FTD and SCA36.

Zachary T McEachin1, Tania F Gendron2, Nisha Raj3, María García-Murias4, Anwesha Banerjee5, Ryan H Purcell3, Patricia J Ward5, Tiffany W Todd6, Megan E Merritt-Garza7, Karen Jansen-West6, Chadwick M Hales8, Tania García-Sobrino9, Beatriz Quintáns4, Christopher J Holler10, Georgia Taylor10, Beatriz San Millán11, Susana Teijeira11, Toru Yamashita12, Ryuichi Ohkubo13, Nicholas M Boulis14, Chongchong Xu15, Zhexing Wen16, Nathalie Streichenberger17, Brent L Fogel18, Thomas Kukar19, Koji Abe12, Dennis W Dickson6, Manuel Arias20, Jonathan D Glass8, Jie Jiang5, Malú G Tansey21, María-Jesús Sobrido4, Leonard Petrucelli2, Wilfried Rossoll2, Gary J Bassell22.   

Abstract

GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and lead to the production of aggregating dipeptide repeat proteins (DPRs) via repeat associated non-AUG (RAN) translation. Here, we show the similar intronic GGCCTG HREs that causes spinocerebellar ataxia type 36 (SCA36) is also translated into DPRs, including poly(GP) and poly(PR). We demonstrate that poly(GP) is more abundant in SCA36 compared to c9ALS/FTD patient tissue due to canonical AUG-mediated translation from intron-retained GGCCTG repeat RNAs. However, the frequency of the antisense RAN translation product poly(PR) is comparable between c9ALS/FTD and SCA36 patient samples. Interestingly, in SCA36 patient tissue, poly(GP) exists as a soluble species, and no TDP-43 pathology is present. We show that aggregate-prone chimeric DPR (cDPR) species underlie the divergent DPR pathology between c9ALS/FTD and SCA36. These findings reveal key differences in translation, solubility, and protein aggregation of DPRs between c9ALS/FTD and SCA36.
Copyright © 2020 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  ALS; C9orf72 expansion; FTD; RAN translation; SCA36; antisense oligonucleotide therapy; chimeric DPRs; dipeptide repeats; neurodegeneration

Mesh：

Substances：

Year:  2020        PMID： 32375063      PMCID： PMC8138626          DOI： 10.1016/j.neuron.2020.04.011

Source DB:  PubMed          Journal:  Neuron        ISSN： 0896-6273            Impact factor:   17.173


  61 in total

1.  Acoustic impairment is a distinguishable clinical feature of Asidan/SCA36.

Authors:  Yoshio Ikeda; Yasuyuki Ohta; Tomoko Kurata; Yoshihiko Shiro; Yoshiki Takao; Koji Abe
Journal:  J Neurol Sci       Date:  2012-11-07       Impact factor: 3.181

2.  Genetic and clinical analysis of spinocerebellar ataxia type 36 in Mainland China.

Authors:  S Zeng; J Zeng; M He; X Zeng; Y Zhou; Z Liu; K Xia; Q Pan; H Jiang; L Shen; X Yan; B Tang; J Wang
Journal:  Clin Genet       Date:  2016-01-20       Impact factor: 4.438

3.  Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins.

Authors:  Kohji Mori; Thomas Arzberger; Friedrich A Grässer; Ilse Gijselinck; Stephanie May; Kristin Rentzsch; Shih-Ming Weng; Martin H Schludi; Julie van der Zee; Marc Cruts; Christine Van Broeckhoven; Elisabeth Kremmer; Hans A Kretzschmar; Christian Haass; Dieter Edbauer
Journal:  Acta Neuropathol       Date:  2013-10-17       Impact factor: 17.088

4.  Two cases of spinocerebellar ataxia accompanied by involvement of the skeletal motor neuron system and bulbar palsy.

Authors:  Yasuyuki Ohta; Takeshi Hayashi; Makiko Nagai; Miyuki Okamoto; Shoko Nagotani; Isao Nagano; Nobuhiko Ohmori; Yasushi Takehisa; Tetsuro Murakami; Mikio Shoji; Tatsushi Kamiya; Koji Abe
Journal:  Intern Med       Date:  2007-06-01       Impact factor: 1.271

5.  Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS.

Authors:  Tania F Gendron; Kevin F Bieniek; Yong-Jie Zhang; Karen Jansen-West; Peter E A Ash; Thomas Caulfield; Lillian Daughrity; Judith H Dunmore; Monica Castanedes-Casey; Jeannie Chew; Danielle M Cosio; Marka van Blitterswijk; Wing C Lee; Rosa Rademakers; Kevin B Boylan; Dennis W Dickson; Leonard Petrucelli
Journal:  Acta Neuropathol       Date:  2013-10-16       Impact factor: 17.088

6.  RAN translation at C9orf72-associated repeat expansions is selectively enhanced by the integrated stress response.

Authors:  Katelyn M Green; M Rebecca Glineburg; Michael G Kearse; Brittany N Flores; Alexander E Linsalata; Stephen J Fedak; Aaron C Goldstrohm; Sami J Barmada; Peter K Todd
Journal:  Nat Commun       Date:  2017-12-08       Impact factor: 14.919

7.  Modelling C9orf72 dipeptide repeat proteins of a physiologically relevant size.

Authors:  Janis Bennion Callister; Sarah Ryan; Joan Sim; Sara Rollinson; Stuart M Pickering-Brown
Journal:  Hum Mol Genet       Date:  2016-12-01       Impact factor: 6.150

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

Authors:  Nobutaka Sakae; Kevin F Bieniek; Yong-Jie Zhang; Kelly Ross; Tania F Gendron; Melissa E Murray; Rosa Rademakers; Leonard Petrucelli; Dennis W Dickson
Journal:  Acta Neuropathol Commun       Date:  2018-07-20       Impact factor: 7.801

9.  Neurodegeneration in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9orf72 is linked to TDP-43 pathology and not associated with aggregated forms of dipeptide repeat proteins.

Authors:  Y Davidson; A C Robinson; X Liu; D Wu; C Troakes; S Rollinson; M Masuda-Suzukake; G Suzuki; T Nonaka; J Shi; J Tian; H Hamdalla; J Ealing; A Richardson; M Jones; S Pickering-Brown; J S Snowden; M Hasegawa; D M A Mann
Journal:  Neuropathol Appl Neurobiol       Date:  2015-12-07       Impact factor: 8.090

10.  Retention of hexanucleotide repeat-containing intron in C9orf72 mRNA: implications for the pathogenesis of ALS/FTD.

Authors:  Michael Niblock; Bradley N Smith; Youn-Bok Lee; Valentina Sardone; Simon Topp; Claire Troakes; Safa Al-Sarraj; Claire S Leblond; Patrick A Dion; Guy A Rouleau; Christopher E Shaw; Jean-Marc Gallo
Journal:  Acta Neuropathol Commun       Date:  2016-02-25       Impact factor: 7.578
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  21 in total

1.  Arginine-rich dipeptide-repeat proteins as phase disruptors in C9-ALS/FTD.

Authors:  Hana M Odeh; James Shorter
Journal:  Emerg Top Life Sci       Date:  2020-12-11

Review 2.  RNA-mediated toxicity in C9orf72 ALS and FTD.

Authors:  Zachary T McEachin; Janani Parameswaran; Nisha Raj; Gary J Bassell; Jie Jiang
Journal:  Neurobiol Dis       Date:  2020-08-21       Impact factor: 5.996

3.  Measuring Repeat-Associated Non-AUG (RAN) Translation.

Authors:  Shaopeng Wang; Shuying Sun
Journal:  Methods Mol Biol       Date:  2022

Review 4.  Nuclear-Import Receptors Counter Deleterious Phase Transitions in Neurodegenerative Disease.

Authors:  Hana M Odeh; Charlotte M Fare; James Shorter
Journal:  J Mol Biol       Date:  2021-08-28       Impact factor: 5.469

Review 5.  Combating deleterious phase transitions in neurodegenerative disease.

Authors:  April L Darling; James Shorter
Journal:  Biochim Biophys Acta Mol Cell Res       Date:  2021-02-05       Impact factor: 4.739

Review 6.  Molecular mechanisms underlying nucleotide repeat expansion disorders.

Authors:  Indranil Malik; Chase P Kelley; Eric T Wang; Peter K Todd
Journal:  Nat Rev Mol Cell Biol       Date:  2021-06-17       Impact factor: 113.915

7.  The alternative initiation factor eIF2A plays key role in RAN translation of myotonic dystrophy type 2 CCUG•CAGG repeats.

Authors:  Solaleh Khoramian Tusi; Lien Nguyen; Kiruphagaran Thangaraju; Jian Li; John D Cleary; Tao Zu; Laura P W Ranum
Journal:  Hum Mol Genet       Date:  2021-05-31       Impact factor: 5.121

8.  Soluble and insoluble dipeptide repeat protein measurements in C9orf72-frontotemporal dementia brains show regional differential solubility and correlation of poly-GR with clinical severity.

Authors:  Annelies Quaegebeur; Idoia Glaria; Tammaryn Lashley; Adrian M Isaacs
Journal:  Acta Neuropathol Commun       Date:  2020-11-09       Impact factor: 7.801

9.  Network analysis of the progranulin-deficient mouse brain proteome reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations.

Authors:  Meixiang Huang; Erica Modeste; Eric Dammer; Paola Merino; Georgia Taylor; Duc M Duong; Qiudong Deng; Christopher J Holler; Marla Gearing; Dennis Dickson; Nicholas T Seyfried; Thomas Kukar
Journal:  Acta Neuropathol Commun       Date:  2020-10-07       Impact factor: 7.578

10.  The carboxyl termini of RAN translated GGGGCC nucleotide repeat expansions modulate toxicity in models of ALS/FTD.

Authors:  Fang He; Brittany N Flores; Amy Krans; Michelle Frazer; Sam Natla; Sarjina Niraula; Olamide Adefioye; Sami J Barmada; Peter K Todd
Journal:  Acta Neuropathol Commun       Date:  2020-08-04       Impact factor: 7.578
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