Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease-Reference-Cited by-同舟云学术

Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease

Published:2018-11-02 Issue:6414 Volume:362 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Kam Tae-In¹²³^ORCID,Mao Xiaobo¹²³^ORCID,Park Hyejin¹²³^ORCID,Chou Shih-Ching¹⁴,Karuppagounder Senthilkumar S.¹²³^ORCID,Umanah George Essien¹²^ORCID,Yun Seung Pil¹²³^ORCID,Brahmachari Saurav¹²³^ORCID,Panicker Nikhil¹²³,Chen Rong¹²³,Andrabi Shaida A.¹²^ORCID,Qi Chen¹²⁵^ORCID,Poirier Guy G.⁶^ORCID,Pletnikova Olga⁷,Troncoso Juan C.²⁷,Bekris Lynn M.⁸^ORCID,Leverenz James B.⁹,Pantelyat Alexander²^ORCID,Ko Han Seok¹²³^ORCID,Rosenthal Liana S.²^ORCID,Dawson Ted M.¹²³⁴¹⁰^ORCID,Dawson Valina L.¹²³¹⁰¹¹^ORCID

Affiliation:

1. Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

3. Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA.

4. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

5. Department of Neurology, Xin Hua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.

6. Centre de recherche du CHU de Québec-Pavillon CHUL, Faculté de Médecine, Université Laval, Québec G1V 4G2, Canada.

7. Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

8. Lerner Research Institute, Genomic Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.

9. Lou Ruvo Center for Brain Health, Neurological Institute, and Department of Neurology, Cleveland Clinic, Cleveland, OH 44195, USA.

10. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

11. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

PAR promotes α-synuclein toxicity How pathologic α-synuclein (α-syn) leads to neurodegeneration in Parkinson's disease (PD) remains poorly understood. Kam et al. studied the α-syn preformed fibril (α-syn PFF) model of sporadic PD (see the Perspective by Brundin and Wyse). They found that pathologic α-syn–activated poly(adenosine 5′-diphosphate–ribose) (PAR) polymerase–1 (PARP-1) and inhibition of PARP or knockout of PARP-1 protected mice from pathology. The generation of PAR by α-syn PFF–induced PARP-1 activation converted α-syn PFF to a strain that was 25-fold more toxic, termed PAR–α-syn PFF. An increase of PAR in the cerebrospinal fluid and evidence of PARP activation in the substantia nigra of PD patients indicates that PARP activation contributes to the pathogenesis of PD through parthanatos and conversion of α-syn to a more toxic strain. Science , this issue p. eaat8407 ; see also p. 521

Funder

National Institute of Neurological Disorders and Stroke

Jane and Lee Seidman Fund

Adrienne Helis Malvin Medical Research Foundation

NIH/National Institute on Aging grant

American Parkinson Disease Association (APDA) Research Grant

JPB Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference30 articles.