Introduction

α-synuclein (SNCA), a major component of Lewy body is a pathological hallmark of Parkinson’s disease (PD). Mutations in the SNCA gene cause misfolding and aggregation of SNCA protein, which results in neurodegeneration. Several studies have established the neuroprotective benefits of β2-adrenoreceptor (β2AR) agonists in PD However, β2AR agonists are associated with peripheral side effects- tachycardia, palpitation, pulmonary edema, myocardial ischemia, and cardiac arrhythmia due to βARactivation in peripheral tissues. PD therapy with β2AR agonists, therefore, warrants a brain-specific delivery.

Area covered

This review highlights the SNCA mediated neurodegenerative pathways in PD and various treatment strategies under investigation to lower SNCA gene expression, primarily focusing on β2AR mediated pathway. The review also discusses the beneficial and side effects of β2AR agonists in PD treatment by reviewing clinical trials, epidemiological studies, and meta-analysis data. Here we depict the need to develop a novel drug delivery system to achieve brain-specific delivery of β2AR agonists to overcome peripheral side effects and also propose various nano delivery strategies to achieve the same.

Expert opinion

Brain targeted delivery of β2AR agonists via various nano delivery systems will significantly downregulate SNCA gene expression in PD and also overcomes peripheral side effects of β2AR agonists.

中文翻译：

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β2肾上腺素受体激动剂的新型药物递送系统可抑制帕金森氏病管理中的SNCA基因表达和线粒体氧化应激。

介绍

路易体的主要成分α-突触核蛋白（SNCA）是帕金森氏病（PD）的病理标志。SNCA基因中的突变会导致SNCA蛋白错误折叠和聚集，从而导致神经变性。几项研究已经建立了β2-肾上腺素能受体（β2AR）激动剂在PD中的神经保护作用。但是，β2AR激动剂与周围组织的副作用有关-心动过速，心pa，肺水肿，心肌缺血和心律不齐，这是由于周围组织中的βAR活化引起的。因此，使用β2AR激动剂进行PD治疗可确保脑部特异性递送。

覆盖面积

这篇综述强调了PD中SNCA介导的神经退行性途径以及正在研究的降低SNCA基因表达的各种治疗策略，主要集中在β2AR介导的途径上。该综述还通过回顾临床试验，流行病学研究和荟萃分析数据，讨论了β2AR激动剂在PD治疗中的有益作用和副作用。在这里，我们描述了开发新型药物递送系统以实现β2AR激动剂的脑特异性递送以克服外周副作用的需求，并且还提出了各种纳米递送策略来实现相同的目的。

专家意见

通过各种纳米递送系统通过脑靶向递送β2AR激动剂将显着下调PD中的SNCA基因表达，并且还克服了β2AR激动剂的周边副作用。