Evidence supporting the use of β2AR agonists in synucleinopathies is rapidly growing. Findings come from different scientific approaches. Molecular and immunological data suggest that adrenergic stimulation may decrease both α-synuclein (α-syn) deposition and pro-inflammatory/neurotoxic molecules release. Small open label clinical trials including a total number of 25 Parkinson’s disease (PD) patients, in which the β2AR agonist salbutamol was added to levodopa, suggest a promising symptomatic benefit. In line with these findings, epidemiological studies investigating the risk of PD development suggest that long term exposure to the agonist salbutamol might be protective, while the antagonist propranolol possibly detrimental. Nonetheless, in both lines of investigation the studies performed so far present important limitations. On the clinical side, large randomized controlled trials are lacking, whereas on the epidemiological side the presence of co-morbid conditions (i.e. smoking and essential tremor) potentially influencing PD risk should taken into consideration. In summary, it is our opinion that β2AR stimulation in synucleinopathies has a rationale and therefore merits further investigation.

Graphical Abstract

中文翻译：

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β2-肾上腺素受体激动剂在帕金森氏病和其他突触核病中的作用。

支持在突触核蛋白病中使用β2AR激动剂的证据正在迅速增长。研究结果来自不同的科学方法。分子和免疫学数据表明，肾上腺素能刺激可同时减少α-突触核蛋白（α-syn）沉积和促炎/神经毒性分子的释放。包括25名帕金森病（PD）患者在内的小型开放标签临床试验表明，将β2AR激动剂沙丁胺醇添加到左旋多巴中，表明有希望的对症治疗。与这些发现一致，流行病学研究调查了PD发展的风险，表明长期暴露于激动剂沙丁胺醇可能具有保护作用，而拮抗剂普萘洛尔则可能有害。但是，在这两个调查领域中，迄今为止进行的研究都存在重要的局限性。在临床方面，尚缺乏大型的随机对照试验，而在流行病学方面，应考虑可能影响PD风险的并存病（即吸烟和原发性震颤）的存在。综上所述，我们认为在突触核蛋白病中β2AR刺激具有基本原理，因此值得进一步研究。

图形概要