C9orf72 poly(GR) aggregation induces TDP-43 proteinopathy

Casey N. Cook; Yanwei Wu; Hana M. Odeh; Tania F. Gendron; Karen Jansen-West; Giulia del Rosso; Mei Yue; Peizhou Jiang; Edward Gomes; Jimei Tong; Lillian M. Daughrity; Nicole M. Avendano; Monica Castanedes-Casey; Wei Shao; Björn Oskarsson; Giulio S. Tomassy; Alexander McCampbell; Frank Rigo; Dennis W. Dickson; James Shorter; Yong-Jie Zhang; Leonard Petrucelli

doi:10.1126/scitranslmed.abb3774

Research ArticleNEURODEGENERATIVE DISORDERS

C9orf72 poly(GR) aggregation induces TDP-43 proteinopathy

View ORCID ProfileCasey N. Cook¹,²,*,
View ORCID ProfileYanwei Wu¹,*,
View ORCID ProfileHana M. Odeh ³,*,
View ORCID ProfileTania F. Gendron ¹,²,
View ORCID ProfileKaren Jansen-West¹,
Giulia del Rosso¹,
Mei Yue¹,
Peizhou Jiang¹,
Edward Gomes³,
Jimei Tong¹,
View ORCID ProfileLillian M. Daughrity¹,
Nicole M. Avendano¹,
View ORCID ProfileMonica Castanedes-Casey¹,
Wei Shao¹,
View ORCID ProfileBjörn Oskarsson⁴,
Giulio S. Tomassy⁵,
View ORCID ProfileAlexander McCampbell⁵,
Frank Rigo⁶,
View ORCID ProfileDennis W. Dickson ¹,²,
View ORCID ProfileJames Shorter ³,†,
View ORCID ProfileYong-Jie Zhang ¹,²,† and
View ORCID ProfileLeonard Petrucelli ¹,²,†

¹Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
²Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.
³Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁴Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA.
⁵Neurology Research, Biogen Idec, Cambridge, MA 02142, USA.
⁶Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.

↵†Corresponding author. Email: petrucelli.leonard{at}mayo.edu (L.P.); zhang.yongjie{at}mayo.edu (Y.-J.Z.); jshorter{at}pennmedicine.upenn.edu (J.S.)

↵* These authors contributed equally to this work.

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Science Translational Medicine 02 Sep 2020:
Vol. 12, Issue 559, eabb3774
DOI: 10.1126/scitranslmed.abb3774

Casey N. Cook

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

2Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.

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Yanwei Wu

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Hana M. Odeh

3Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Tania F. Gendron

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

2Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.

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Karen Jansen-West

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Giulia del Rosso

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Mei Yue

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Peizhou Jiang

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Edward Gomes

3Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Jimei Tong

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Lillian M. Daughrity

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Nicole M. Avendano

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Monica Castanedes-Casey

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Wei Shao

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

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Björn Oskarsson

4Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA.

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Giulio S. Tomassy

5Neurology Research, Biogen Idec, Cambridge, MA 02142, USA.

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Alexander McCampbell

5Neurology Research, Biogen Idec, Cambridge, MA 02142, USA.

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Frank Rigo

6Ionis Pharmaceuticals, Carlsbad, CA 92010, USA.

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Dennis W. Dickson

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

2Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.

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James Shorter

3Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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For correspondence: petrucelli.leonard@mayo.edu zhang.yongjie@mayo.edu jshorter@pennmedicine.upenn.edu

Yong-Jie Zhang

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

2Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.

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For correspondence: petrucelli.leonard@mayo.edu zhang.yongjie@mayo.edu jshorter@pennmedicine.upenn.edu

Leonard Petrucelli

1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.

2Neurobiology of Disease Graduate Program, Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.

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For correspondence: petrucelli.leonard@mayo.edu zhang.yongjie@mayo.edu jshorter@pennmedicine.upenn.edu

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C9orf72 poly(GR) aggregation induces TDP-43 proteinopathy

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