Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson’s disease

Zhong-Can Chen; Wei Zhang; Ling-Ling Chua; Chou Chai; Rong Li; Lin Lin; Zhen Cao; Dario C. Angeles; Lawrence W. Stanton; Jian-He Peng; Zhi-Dong Zhou; Kah-Leong Lim; Li Zeng; Eng-King Tan

doi:10.1126/scisignal.aam6790

Research ArticleNeurodegeneration

Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson’s disease

Zhong-Can Chen¹,
Wei Zhang¹,
Ling-Ling Chua²,
Chou Chai³,
Rong Li⁴,
Lin Lin⁵,⁶,
Zhen Cao¹,
Dario C. Angeles²,*,
Lawrence W. Stanton⁵,
Jian-He Peng⁴,†,
Zhi-Dong Zhou²,⁷,
Kah-Leong Lim³,⁷,⁸,
Li Zeng¹,⁷,‡, and
Eng-King Tan²,⁷,⁹,‡

¹Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.
²Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.
³Neurodegeneration Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.
⁴Analytical Mass Spectrometry Laboratory, Experimental Therapeutics Centre, Agency of Science, Technology and Research (A*STAR), Singapore 138669, Singapore.
⁵Stem Cell and Developmental Biology Group, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
⁶National University of Singapore (NUS) Graduate School for Integrative Sciences and Engineering, NUS, Singapore 117456, Singapore.
⁷Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.
⁸Department of Physiology, Yong Loo Lin School of Medicine, NUS, Singapore 117597, Singapore.
⁹Department of Neurology, National Neuroscience Institute, SGH Campus, Singapore 169856, Singapore.

↵‡Corresponding author. Email: li_zeng{at}nni.com.sg (L.Z.); tan.eng.king{at}sgh.com.sg (E.-K.T.)

↵* Present address: Department of Paediatrics and Psychology, #15-01 MD1, 12 Science Drive 2, Yong Loo Lin School of Medicine, NUS, Singapore 117549, Singapore.
↵† Present address: National Collection of Type Cultures, Public Health England, London NW95HT, UK.

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Science Signaling 18 Jul 2017:
Vol. 10, Issue 488, eaam6790
DOI: 10.1126/scisignal.aam6790

Zhong-Can Chen

Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

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Wei Zhang

Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

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Ling-Ling Chua

Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.

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Chou Chai

Neurodegeneration Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

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Rong Li

Analytical Mass Spectrometry Laboratory, Experimental Therapeutics Centre, Agency of Science, Technology and Research (A*STAR), Singapore 138669, Singapore.

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Lin Lin

Stem Cell and Developmental Biology Group, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.

National University of Singapore (NUS) Graduate School for Integrative Sciences and Engineering, NUS, Singapore 117456, Singapore.

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Zhen Cao

Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

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Dario C. Angeles

Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.

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Lawrence W. Stanton

Stem Cell and Developmental Biology Group, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.

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Jian-He Peng

Analytical Mass Spectrometry Laboratory, Experimental Therapeutics Centre, Agency of Science, Technology and Research (A*STAR), Singapore 138669, Singapore.

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Zhi-Dong Zhou

Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.

Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.

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Kah-Leong Lim

Neurodegeneration Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.

Department of Physiology, Yong Loo Lin School of Medicine, NUS, Singapore 117597, Singapore.

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Li Zeng

Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.

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For correspondence: Li_Zeng@nni.com.sg tan.eng.king@sgh.com.sg

Eng-King Tan

Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.

Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.

Department of Neurology, National Neuroscience Institute, SGH Campus, Singapore 169856, Singapore.

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For correspondence: Li_Zeng@nni.com.sg tan.eng.king@sgh.com.sg

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vol. 10 no. 488

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https://doi.org/10.1126/scisignal.aam6790

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Received December 29, 2016
Accepted June 30, 2017
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Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works http://www.sciencemag.org/about/science-licenses-journal-article-reuseThis is an article distributed under the terms of the Science Journals Default License.

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Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson’s disease

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