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Wednesday
Sep272017

Commonly used asthma medications appear to regulate epigenetic mechanisms and may be associated with decreased risk for Parkinson’s disease

Arrows indicate Lew bodies, arrowheads, Lewy neuritesIn an interesting new study, β2-adrenoreceptor ligands were found to regulate the α-synuclein gene (SNCA) via epigenetic mechanisms [1].  Further, prolonged use of the asmtha medication salbutamol, which is a β2-adrenoreceptor agonist, was linked to reduced risk associated with Parkinson’s disease [1]. Results from the study demonstrated that the β2-adrenoreceptor regulates histone H3 acetylation and DNA replication in the cell, controlling the amount of α-synuclein [1,2]. Lewy bodies, one of the neural hallmarks of Parkinson’s, are protein aggregates mainly formed from α-synuclein. Lewy bodies are connected to the death of neuronal cells as they are mainly found in brain areas where the most severe neuronal loss is seen [3]. Thus decreasing the amount of α-synuclein in neuronal cells is thought be one way to potentially prevent Parkinson's disease.

After a compound screen, the researchers identified four that reduced SNCA gene activity in human cells and further tests showed that β2-adrenoreceptor agonists led to reduced H3 acetylation, SNCA expression, and the amount of α-synuclein in both cell culture and in animal studies [1]. These results prompted researchers ask whether β2-adrenoreceptor agonist or antagonist medications might influence the prevalence of Parkinson’s disease. By studying the medical records of nearly 5 million Norwegians, they found that those with long term use of salbutamol for their asthma, had lower risk of Parkinson’s, whereas people using propranolol for heart conditions appeared to have increased risk [1]. These findings suggest that the β2-adrenoreceptor may play a role in Parkinson’s disease and opens new doors for Parkinson’s disease research. Perhaps in the future Parkinson’s could be treated, or even pre-treated using epigenetic drugs.

                                                                                                                                            

-JKR-

 

[1] Mittal S, Bjørnevik K, Im DS, Flierl A, Dong X, Locascio JJ, Abo KM, Long E, Jin M, Xu B, Xiang YK, Rochet JC, Engeland A, Rizzu P, Heutink P, Bartels T, Selkoe DJ, Caldarone BJ, Glicksman MA, Khurana V, Schüle B, Park DS, Riise T, Scherzer CR: β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson's disease. Science. 2017;357(6354):891-98

[2] Bannister AJ, Kouzarides T: Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381-95

[3] Michael J. Fox Foundation for Parkinson’s Research: Alpha-synuclein and Parkinson's Disease. https://www.michaeljfox.org/understanding-parkinsons/living-with-pd/topic.php?alpha-synuclein

Image: Ingelsson M (2016) Alpha-Synuclein Oligomers—Neurotoxic Molecules in Parkinson's Disease and Other Lewy Body Disorders. Front. Neurosci. 10:408. doi: 10.3389/fnins.2016.00408

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