LRRK2 activation in idiopathic Parkinson’s disease

Roberto Di Maio; Eric K. Hoffman; Emily M. Rocha; Matthew T. Keeney; Laurie H. Sanders; Briana R. De Miranda; Alevtina Zharikov; Amber Van Laar; Antonia F. Stepan; Thomas A. Lanz; Julia K. Kofler; Edward A. Burton; Dario R. Alessi; Teresa G. Hastings; J. Timothy Greenamyre

doi:10.1126/scitranslmed.aar5429

Research ArticleParkinson’s Disease

LRRK2 activation in idiopathic Parkinson’s disease

Roberto Di Maio ¹,²,³,
Eric K. Hoffman¹,²,
Emily M. Rocha¹,²,
Matthew T. Keeney¹,²,
Laurie H. Sanders¹,²,⁴,
Briana R. De Miranda¹,²,
Alevtina Zharikov¹,²,
Amber Van Laar¹,²,
Antonia F. Stepan⁵,
Thomas A. Lanz⁵,
Julia K. Kofler⁶,
Edward A. Burton¹,²,⁷,
Dario R. Alessi ⁸,
Teresa G. Hastings¹,² and
J. Timothy Greenamyre¹,²,⁷,*

¹Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.
²Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
³Ri.MED Foundation, Palermo, Italy.
⁴Department of Neurology, Duke University, Durham, NC 27710, USA.
⁵Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA.
⁶Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
⁷Geriatric Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA 15240, USA.
⁸MRC Protein Phosphorylation and Ubiquitylation Units, University of Dundee, Dundee, Scotland.

↵*Corresponding author. Email: jgreena{at}pitt.edu

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Science Translational Medicine 25 Jul 2018:
Vol. 10, Issue 451, eaar5429
DOI: 10.1126/scitranslmed.aar5429

Roberto Di Maio

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.Ri.MED Foundation, Palermo, Italy.

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Eric K. Hoffman

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Emily M. Rocha

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Matthew T. Keeney

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Laurie H. Sanders

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Briana R. De Miranda

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Alevtina Zharikov

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Amber Van Laar

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Antonia F. Stepan

Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA.

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Thomas A. Lanz

Worldwide Medicinal Chemistry, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA.

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Julia K. Kofler

Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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Edward A. Burton

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Dario R. Alessi

MRC Protein Phosphorylation and Ubiquitylation Units, University of Dundee, Dundee, Scotland.

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Teresa G. Hastings

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

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J. Timothy Greenamyre

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For correspondence: jgreena@pitt.edu

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Wild-type LRRK2 is activated in nigrostriatal dopamine neurons in idiopathic Parkinson’s disease and plays a pathogenic role in this neurodegenerative disorder.

LRRK2 activation in idiopathic Parkinson’s disease

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