{beta}2-Adrenoreceptor is a regulator of the {alpha}-synuclein gene driving risk of Parkinsons disease

Copy number mutations implicate excess production of α-synuclein as a possibly causative factor in Parkinson’s disease (PD). Using an unbiased screen targeting endogenous gene expression, we discovered that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene (SNCA). β2AR ligands modulate SNCA transcription through histone 3 lysine 27 acetylation of its promoter and enhancers. Over 11 years of follow-up in 4 million Norwegians, the β2AR agonist salbutamol, a brain-penetrant asthma medication, was associated with reduced risk of developing PD (rate ratio, 0.66; 95% confidence interval, 0.58 to 0.76). Conversely, a β2AR antagonist correlated with increased risk. β2AR activation protected model mice and patient-derived cells. Thus, β2AR is linked to transcription of α-synuclein and risk of PD in a ligand-specific fashion and constitutes a potential target for therapies.

Source: ScienceNOW - August 31, 2017 Category: Science Authors: Mittal, S., Bjornevik, K., Im, D. S., Flierl, A., Dong, X., Locascio, J. J., Abo, K. M., Long, E., Jin, M., Xu, B., Xiang, Y. K., Rochet, J.-C., Engeland, A., Rizzu, P., Heutink, P., Bartels, T., Selkoe, D. J., Caldarone, B. J., Glicksman, M. A., Khurana, Tags: Genetics r-articles Source Type: news