Novel drug delivery systems of beta 2 adrenoreceptor agonists to suppress SNCA gene expression and mitochondrial oxidative stress in Parkinson's disease management

摘要

Introduction alpha-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 beta 2-adrenoreceptor (beta 2AR) agonists in PD However, beta 2AR agonists are associated with peripheral side effects- tachycardia, palpitation, pulmonary edema, myocardial ischemia, and cardiac arrhythmia due to beta ARactivation in peripheral tissues. PD therapy with beta 2AR 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 beta 2AR mediated pathway. The review also discusses the beneficial and side effects of beta 2AR 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 beta 2AR agonists to overcome peripheral side effects and also propose various nano delivery strategies to achieve the same. Expert opinion Brain targeted delivery of beta 2AR agonists via various nano delivery systems will significantly downregulate SNCA gene expression in PD and also overcomes peripheral side effects of beta 2AR agonists.