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

Shuchi Mittal(Brigham and Women's Hospital), Kjetil Bjørnevik(Haukeland University Hospital), Doo Soon Im(MIND Research Institute), Adrian Flierl(Parkinson's Institute and Clinical Center), Xianjun Dong(Brigham and Women's Hospital), Joseph J. Locascio(Brigham and Women's Hospital), Kristine M. Abo(Brigham and Women's Hospital), Elizabeth Long(Brigham and Women's Hospital), Ming Jin(Brigham and Women's Hospital), Bing Xu(University of California, Davis), Yang K. Xiang(University of California, Davis), Jean‐Christophe Rochet(Purdue University West Lafayette), Anders Engeland(Norwegian Institute of Public Health), Patrizia Rizzu(German Center for Neurodegenerative Diseases), Peter Heutink(German Center for Neurodegenerative Diseases), Tim Bartels(Brigham and Women's Hospital), Dennis J. Selkoe(Brigham and Women's Hospital), Barbara J. Caldarone(Brigham and Women's Hospital), Marcie A. Glicksman(Harvard NeuroDiscovery Center), Vikram Khurana(Brigham and Women's Hospital), Birgitt Schüle(Parkinson's Institute and Clinical Center), David S. Park(MIND Research Institute), Trond Riise(Haukeland University Hospital), Clemens R. Scherzer(Brigham and Women's Hospital)
Science
August 31, 2017
10.1126/science.aaf3934
Cited by 434Open Access
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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

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