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: Ru-Huei Fu, Yu-Chi Wang, Chang-Shi Chen, Rong-Tzong Tsai, Shih-Ping Liu, Wen-Lin Chang, Hsin-Lien Lin, Chia-Hui Lu, Jing-Rong Wei, Zih-Wan Wang, Woei-Cherng Shyu, Shinn-Zong Lin
• Journal: Neuropharmacology (Neuropharmacology) Vol. 82 Pg. 108-20 (Jul 2014) ISSN: 1873-7064 [Electronic] England
• PMID: 23973292 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antiparkinson Agents
• Berberine Alkaloids
• Caenorhabditis elegans Proteins
• EGL-1 protein, C elegans
• Repressor Proteins
• SNCA protein, human
• acetylcorynoline
• alpha-Synuclein
• Green Fluorescent Proteins
• Oxidopamine
• Dopamine

Topics

• Animals
• Animals, Genetically Modified
• Antiparkinson Agents (chemistry, pharmacology)
• Appetitive Behavior (drug effects)
• Berberine Alkaloids (chemistry, pharmacology)
• Caenorhabditis elegans
• Caenorhabditis elegans Proteins (metabolism)
• Dopamine (metabolism)
• Dopaminergic Neurons (drug effects, physiology)
• Green Fluorescent Proteins (genetics)
• Humans
• Molecular Structure
• Muscle Cells (drug effects, physiology)
• Nerve Degeneration (drug therapy, physiopathology)
• Oxidopamine
• Parkinsonian Disorders (drug therapy, physiopathology)
• Repressor Proteins (metabolism)
• alpha-Synuclein (genetics, metabolism)