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PLoS One. 2014 Jan 8;9(1):e85305. doi: 10.1371/journal.pone.0085305. eCollection 2014.

n-butylidenephthalide protects against dopaminergic neuron degeneration and α-synuclein accumulation in Caenorhabditis elegans models of Parkinson's disease.

Author information

1
Graduate Institute of Immunology, China Medical University, Taichung, Taiwan ; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan.
2
Department of Pathology, China Medical University Hospital, Taichung, Taiwan.
3
Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan ; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
4
Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan.
5
Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
6
Graduate Institute of Immunology, China Medical University, Taichung, Taiwan ; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan ; Department of Neurosurgery, China Medical University Beigang Hospital, Yunlin, Taiwan ; Department of Neurosurgery, Tainan Municipal An-Nan Hospital-China Medical University, Tainan, Taiwan.
7
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.

Abstract

BACKGROUND:

Parkinson'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 FINDINGS:

In 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.

PMID:
24416384
PMCID:
PMC3885701
DOI:
10.1371/journal.pone.0085305
[Indexed for MEDLINE]
Free PMC Article

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