I. Evaluation of the effect of acetylcorynoline in Caenorhabditis elegans models of Parkinson's diseaseII. Developing the microinjection technology of Caenorhabditis elegans

Autor: Wen-Lin Chang, 張文琳
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 102
I. Evaluation of the effect of acetylcorynoline in Caenorhabditis elegans models of Parkinson’s disease Parkinson’s disease (PD) is the second most common neurodegenerative disease. It impairs motor skills and cognitive function. Now, the drugs provided only symptomatic relief for PD treatment. The identification of new drugs that reveal benefit in slowing the decline seen in PD patients is the focus of much present research. Acetylcorynoline, the major alkaloid component, derived from Corydalis bungeana, a traditional Chinese medical herb. It has been indicated to have anti-inflammatory properties, but no studies have yet described the effects of Acetylcorynoline on PD. The purpose of this study was to evaluate the potential for Acetylcorynoline to improve PD in Caenorhabditis elegans models. In the current study, we imploy a pharmacological strain (BZ555) that expresses green fluorescent protein specifically in dopaminergic neurons, and a transgenic strain (OW13) that expresses human a-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 reduces dopaminergic neuron degeneration induced by 6-hydroxydopamine in BZ555 strain; blocks α-synuclein aggregation; restores lipid content in OW13 strain; recovers 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 inhibiting egl-1 expression to destroy apoptosis pathways and by raising rpn5 expression to enhance the activity of proteasomes. II. Developing microinjection technology of Caenorhabditis elegans Currently, geneticists use specific genes expression to produce animal models of human diseases by exact transgenic technology. Caenorhabditis elegans has many advantages as an animal model. It has been used widely for studies of developmental genetics. The cell lineage of the entire worm and germline structures are well known. It is inexpensive and easy for transgenic operation. It has short life cycle and the transparent body is observed easily. In the future, we want to use Caenorhabditis elegans to develop the animal model of neurodegenerative diseases by microinjection.
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