title: Acetylcorynoline attenuates dopaminergic neuron degeneration and α-synuclein aggregation in animal models of Parkinson's disease.
abstract: Parkinson's disease (PD), the second most common neurodegenerative disease, impairs motor skills and cognitive function. To date, the drugs used for PD treatment provide only symptomatic relief. The identification of new drugs that show benefit in slowing the decline seen in PD patients is the focus of much current research. Acetylcorynoline is the major alkaloid component derived from Corydalis bungeana, a traditional Chinese medical herb. It has been shown to have anti-inflammatory properties, but no studies have yet described the effects of acetylcorynoline on PD. The aim of this study was to evaluate the potential for acetylcorynoline to improve PD in Caenorhabditis elegans models. In the present study, we used a pharmacological strain (BZ555) that expresses green fluorescent protein specifically in dopaminergic neurons, and a transgenic strain (OW13) that expresses human α-synuclein in muscle cells to study the antiparkinsonian effects of acetylcorynoline. Our experimental data showed that treatment with up to 10 mM acetylcorynoline does not cause toxicity in animals. Acetylcorynoline significantly decreases dopaminergic neuron degeneration induced by 6-hydroxydopamine in BZ555 strain; prevents α-synuclein aggregation; recovers lipid content in OW13 strain; restores food-sensing behavior, and dopamine levels; and prolongs life-span in 6-hydroxydopamine-treated N2 strain, thus showing its potential as a possible antiparkinsonian drug. Acetylcorynoline may exert its effects by decreasing egl-1 expression to suppress apoptosis pathways and by increasing rpn5 expression to enhance the activity of proteasomes.
authors: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan. Electronic address: rhfu@mail.cmu.edu.tw.
authors: Ru-Huei
authors: RH
authors: Fu
authors: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors: Yu-Chi
authors: YC
authors: Wang
authors: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan.
authors: Chang-Shi
authors: CS
authors: Chen
authors: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors: Rong-Tzong
authors: RT
authors: Tsai
authors: Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors: Shih-Ping
authors: SP
authors: Liu
authors: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors: Wen-Lin
authors: WL
authors: Chang
authors: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors: Hsin-Lien
authors: HL
authors: Lin
authors: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors: Chia-Hui
authors: CH
authors: Lu
authors: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors: Jing-Rong
authors: JR
authors: Wei
authors: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors: Zih-Wan
authors: ZW
authors: Wang
authors: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan; Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan.
authors: Woei-Cherng
authors: WC
authors: Shyu
authors: 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. Electronic address: shinnzong@yahoo.com.tw.
authors: Shinn-Zong
authors: SZ
authors: Lin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000978:Antiparkinson Agents / Q000737:chemistry / Q000494:pharmacology*; D001070:Appetitive Behavior / Q000187:drug effects; D001600:Berberine Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D015394:Molecular Structure; D032342:Muscle Cells / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D012097:Repressor Proteins / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D001600:Berberine Alkaloids; D029742:Caenorhabditis elegans Proteins; C112486:EGL-1 protein, C elegans; D012097:Repressor Proteins; C497604:SNCA protein, human; C487645:acetylcorynoline; D051844:alpha-Synuclein; D049452:Green Fluorescent Proteins; D016627:Oxidopamine; D004298:Dopamine
keywords: Acetylcorynoline; Caenorhabditis elegans; Dopaminergic neurons; Parkinson's disease; Proteasome; α-Synuclein