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

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. Drosophila melanogaster with PTEN induced kinase 1 (PINK1) mutations, a prototype PD model, was used in this study. We found that calcium chelation profoundly alleviated a spectrum of PD symptoms. Whereas, calcium supplementation made the case worse, suggesting accumulated calcium contributes to progression of PD. β-asarone administration decreased Ca²⁺ level in PD flies, accompanied by alleviated behavioral and neural defects. Further study demonstrated that β-asarone downregulated L-type Ca²⁺ channels (Dmca1D), which was increased in PD flies. Besides, β-asarone decreased expression of 1,4,5 - trisphosphate receptor (Itpr), 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 in PD flies. While overexpression of Itpr aggravated PD symptoms. The results indicated that increased intracellular calcium influx and release triggers dysregulation of calcium homeostasis in PD flies. And β-asarone prevents PD by restoring Ca²⁺ homeostasis. Overall, the study demonstrated that β-asarone can serve as a new prospective medication against PD or other diseases associated with dysregulation of Ca²⁺ homeostasis.