Abstract
BackgroundParkinson's disease (PD) is the second most common degenerative disorder of the central nervous system that impairs motor skills and cognitive function. To date, the disease has no effective therapies. The identification of new drugs that provide benefit in arresting the decline seen in PD patients is the focus of much recent study. However, the lengthy time frame for the progression of neurodegeneration in PD increases both the time and cost of examining potential therapeutic compounds in mammalian models. An alternative is to first evaluate the efficacy of compounds in Caenorhabditis elegans models, which reduces examination time from months to days. n-Butylidenephthalide is the naturally-occurring component derived from the chloroform extract of Angelica sinensis. It has been shown to have anti-tumor and anti-inflammatory properties, but no reports have yet described the effects of n-butylidenephthalide on PD. The aim of this study was to assess the potential for n-butylidenephthalide to improve PD in C. elegans models.Methodology/Principal FindingsIn the current study, we employed a pharmacological strain that expresses green fluorescent protein specifically in dopaminergic neurons (BZ555) and a transgenic strain that expresses human α-synuclein in muscle cells (OW13) to investigate the antiparkinsonian activities of n-butylidenephthalide. Our results demonstrate that in PD animal models, n-butylidenephthalide significantly attenuates dopaminergic neuron degeneration induced by 6-hydroxydopamine; reduces α-synuclein accumulation; recovers lipid content, food-sensing behavior, and dopamine levels; and prolongs life-span of 6-hydroxydopamine treatment, thus revealing its potential as a possible antiparkinsonian drug. n-Butylidenephthalide may exert its effects by blocking egl-1 expression to inhibit apoptosis pathways and by raising rpn-6 expression to enhance the activity of proteasomes.Conclusions/Significance n-Butylidenephthalide may be one of the effective neuroprotective agents for PD.
Highlights
Parkinson’s disease (PD) is the second most common disorder of the central nervous system, the incidence of which quickly augments in the people over the age of 60 years
To assess the effects of n-butylidenephthalide on DA neuron degeneration and a-synuclein accumulation, we first determined the optimal concentrations of n-butylidenephthalide to evaluate in our C. elegans PD models by food clearance test
The addition of 2 mM or 5 mM n-butylidenephthalide to the cultures containing N2, BZ555 or OW13 strains showed no effect on food clearance compared to that in control animals, whereas animals treated to 10 mM or 20 mM n-butylidenephthalide had significantly delayed food clearance (Figure 2A)
Summary
Parkinson’s disease (PD) is the second most common disorder of the central nervous system, the incidence of which quickly augments in the people over the age of 60 years. In PD, the accumulation of a-synuclein is a critical challenge to DA neurons, especially as they aggregate in inclusions and destroy the cellular machinery required for their degradation. These influences may be compounded by PD-related dysregulation of chaperones [5], a continually accelerating loss in general cellular homeostasis [6,7]. Parkinson’s disease (PD) is the second most common degenerative disorder of the central nervous system that impairs motor skills and cognitive function. The aim of this study was to assess the potential for n-butylidenephthalide to improve PD in C. elegans models
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