β-asarone relieves Parkinson’s disease through reducing intracellular Ca2+ in PINK1 mutant Drosophila melanogaster

Abstract

Abstract β-asarone, an effective volatile oil component of Acorus chinensis, has been found to hold beneficial effects on Parkinson's disease (PD), but its mechanism remains incompletely understood. Ca2+ dys-homeostasis in dopaminergic neurons underlies the pathology of PD, thus this study aims to investigate whether β-asarone protects against PD by modulating Ca2+ level. Drosophila melanogaster with PINK1 (PTEN induced putative kinase 1) mutations, a prototype PD model, was used in this study. We found that calcium chelation in the diet profoundly alleviated a spectrum of PD symptoms in Drosophila. Whereas, calcium supplementation made the case worse, suggesting accumulated calcium contributes to progression of PD. β-asarone administration decreased calcium level in PD flies, accompanied by alleviated behavioral and neural defects. Further study demonstrated that β-asarone downregulated Dmca1D, a gene encodes L-type Ca2+ channel, which was increased in PD flies. Besides, β-asarone decreased expression of Itpr (1,4,5 - trisphosphate receptor, also known as IP3R), which is responsible for calcium release from endoplasmic reticulum (ER). Knockdown of either Dmca1D or Itpr specifically in dopaminergic neurons alleviated behavioral and neural defects effects in PD flies. While, overexpression of Itpr aggravated PD symptoms. The results indicated that increased calcium influx and intracellular release triggered calcium dyshomeostasis in PD flies. And β-asarone protected against PD by restoring calcium homeostasis. Overall, the study demonstrated that β-asarone can serve as a promising nutritional intervention of PD or other calcium dyshomeostasis related biological events.