β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease-Reference-Cited by-同舟云学术

β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease

Published:2017-09 Issue:6354 Volume:357 Page:891-898
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Mittal Shuchi¹²³^ORCID,Bjørnevik Kjetil⁴⁵^ORCID,Im Doo Soon⁶^ORCID,Flierl Adrian⁷,Dong Xianjun¹²³,Locascio Joseph J.¹⁸^ORCID,Abo Kristine M.¹^ORCID,Long Elizabeth¹^ORCID,Jin Ming²³^ORCID,Xu Bing⁹,Xiang Yang K.⁹,Rochet Jean-Christophe¹⁰^ORCID,Engeland Anders⁴¹¹^ORCID,Rizzu Patrizia¹²,Heutink Peter¹²^ORCID,Bartels Tim²³,Selkoe Dennis J.²³,Caldarone Barbara J.³¹³,Glicksman Marcie A.¹³,Khurana Vikram²³¹⁴,Schüle Birgitt⁷,Park David S.⁶^ORCID,Riise Trond⁴⁵,Scherzer Clemens R.¹²³^ORCID

Affiliation:

1. Neurogenomics Laboratory and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.

2. Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.

3. Department of Neurology, Brigham and Women’s Hospital, Boston, MA 02115, USA.

4. Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

5. The Norwegian Multiple Sclerosis Competence Center, Department of Neurology, Haukeland University Hospital, Norway.

6. Brain and Mind Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.

7. The Parkinson’s Institute and Clinical Center, Sunnyvale, CA 94085, USA.

8. Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.

9. Department of Pharmacology, University of California at Davis, Davis, CA 95616, USA.

10. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.

11. Department of Pharmacoepidemiology, Norwegian Institute of Public Health, Oslo, Norway.

12. German Center for Neurodegenerative Diseases (DZNE), Tübingen 72076, Germany.

13. Harvard NeuroDiscovery Center, Harvard Medical School, Boston, MA 02115, USA.

14. Harvard Stem Cell Institute, Cambridge, MA 02138, USA.

Abstract

Elucidating the risk of Parkinson's disease High expression of the α-synuclein gene ( SNCA ) is a risk factor for Parkinson's disease (PD), but certain drugs may mitigate this risk. Mittal et al. ran a small-molecule screen to identify compounds that regulate levels of SNCA expression and found that several β2-adrenoreceptor (β2AR) agonists reduced them (see the Perspective by Snyder). These compounds modulated epigenetic marks at the SNCA gene, effectively suppressing SNCA transcription. The authors looked at the pharmaceutical history of more than 4 million Norwegians over an 11-year period and found a reduced risk of PD among those that were taking one of the β2AR agonists for other medical problems. Science , this issue p. 891 ; see also p. 869

Funder

National Institute of Neurological Disorders and Stroke

Michael J. Fox Foundation for Parkinson’s Research

Multiple System Atrophy Coalition

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference36 articles.

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