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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 沈立言(Lee-Yan Sheen) | |
| dc.contributor.author | Yu-En Lin | en |
| dc.contributor.author | 林毓恩 | zh_TW |
| dc.date.accessioned | 2022-11-25T03:04:12Z | - |
| dc.date.available | 2026-08-01 | |
| dc.date.copyright | 2021-11-09 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-02 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81813 | - |
| dc.description.abstract | 帕金森氏症為常見的老化型神經退行性疾病之一，迄今仍缺乏有效的預防與治療方法。因此，尋找替代或互補的治療方法是迫切需要的。天麻（Gastrodia elata Blume）係蘭科植物之塊莖，為傳統中醫藥常用的食療素材，同時亦屬於臺灣衛福部可供食品原料公告之草本植物。傳統上已被用於治療癲癇，頭暈和偏頭痛等神經系統疾病，也對毒素誘導的帕金森氏症模式具有神經保護和抗發炎作用。然而，天麻在神經保護機制方面，針對特定帕金森氏症之治療，是否具有藥物指導下之互補性，以及發展為替代性功能食品之潛力等仍然不清楚。帕金森氏症的大多數病例雖是屬於偶發性的，但亦有10%帕金森氏症起因於家族性遺傳的基因變異。富含白胺酸重複激酶2號（LRRK2-G2019S）基因錯義突變是帕金森氏症最常見之體染色體顯性家族性和偶發性變異，其臨床症狀上也顯現典型症狀。根據先前所建立之研究顯示，果蠅表達Lrrk2-G2019S會產生神經樹突退化、多巴胺神經元喪失及運動缺失。在本研究中我們發現餵食Lrrk2-G2019S果蠅 0.1%（w/w）的天麻，能夠有效防止運動能力的缺失，並且降低成年果蠅腦中多巴胺神經元的喪失。我們進一步研究天麻保護多巴胺神經元的分子機制，發現天麻不僅可以抑制Lrrk2-G2019S蛋白質的堆積及過度活化，同時亦可活化腦部膠細胞中Akt/GSK3β/Nrf2訊息路徑，促進果蠅大腦神經元的存活。我們更利用基因交互作用之實驗，證明大量活化膠細胞之Nrf2本身即具有改善因神經表達Lrrk2-G2019S所引致之運動缺失及多巴胺神經元喪失。我們發現膠細胞中Nrf2之活化可拮抗Lrrk2-G2019S所引致之BMP/Mad 訊息傳遞，以達到神經保護之功效。我們進一步使用G2019S之基因轉殖小鼠模式來驗證天麻在果蠅模式中的機制，結果顯示餵食天麻可以改善G2019S小鼠之運動障礙及保護多巴胺神經元之損傷。藉由檢測小鼠腦部之蛋白質訊息傳遞路徑，我們發現餵食天麻可以抑制Lrrk2-G2019S之堆積及過度活化，同時減緩TGF-β/Smad2/3（與果蠅之BMP/Mad在演化上同源）訊息傳遞來達到神經保護之效，而此保護機制在果蠅和小鼠十分吻合。綜合上述，我們的結果顯示天麻可以藉由活化膠細胞之Nrf2訊息傳遞來保護及改善Lrrk2-G2019S動物模式中的多巴胺神經元死亡與運動障礙。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T03:04:12Z (GMT). No. of bitstreams: 1 U0001-0208202115333100.pdf: 29593879 bytes, checksum: 7c663624973c5283290636921d41ad45 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "Table of Contents Chinese Abstract ............................................................................................................ I Abstract ........................................................................................................................ III Table of Contents .......................................................................................................... V List of Figure .............................................................................................................VIII List of Table ................................................................................................................. XI 1. INTRODUCTION ............................................................................................... 1 2. LITERATURE REVIEW ................................................................................... 4 2.1. Parkinson’s disease (PD) ........................................................................... 4 2.1.1. Basal ganglia circuitry and DA in motor control ............................... 5 2.1.2. Symptoms and clinical diagnosis of PD ............................................. 7 2.1.3. The staging of PD ............................................................................... 9 2.1.4. Epidemiology of PD ......................................................................... 10 2.1.5. Environmental contributors to PD .................................................... 11 2.1.6. Genetics of PD .................................................................................. 17 2.1.7. PARK8, Leucine-rich Repeat Kinase 2 (LRRK2) ............................. 19 2.1.8. Therapies of PD ................................................................................ 25 2.1.9. Traditional Chinese Medicine (TCM) and PD .................................. 26 2.2. Gastrodia elata Blume (GE) ....................................................................... 28 2.2.1. Phytochemistry and pharmacological potential of GE ..................... 30 2.3. Animal models of PD ................................................................................... 35 2.3.1. Drosophila melanogaster model of PD ........................................ 36 2.3.2. GAL4-UAS system ........................................................................ 38 3. AIMS, HYPOTHESES, AND OBJECTIVES ................................................ 40 3.1. Background and problems ....................................................................... 40 3.2. Aims and hypotheses ............................................................................... 40 3.3. Objectives ................................................................................................ 41 4. MATERIALS AND METHODS ..................................................................... 43 4.1. Drosophila stocks and maintenance ........................................................ 43 4.2. Plant material ........................................................................................... 43 4.3. Preparation of WGE and related chemical compounds ........................... 44 4.4. Determination of the active components in the WGE ............................. 45 4.5. Climbing assay ......................................................................................... 45 4.6. Walking assay .......................................................................................... 46 4.7. Immunostaining of whole-mount adult brains ......................................... 46 4.8. Immunoblotting of fly brain lysates ......................................................... 48 4.9. ARE-GFP reporter assay .......................................................................... 49 4.10. Animal care and treatments .................................................................... 50 4.11. Behavioral assays ................................................................................... 50 4.12. Immunohistochemical staining of mice brains ....................................... 51 4.13. Immunoblotting of mice brain ................................................................ 51 4.14. Data analysis ........................................................................................... 52 5. RESULTS ............................................................................................................ 53 6. DISSCUSSION .................................................................................................. 131 7. CONCLUSION ................................................................................................. 158 8. ABBREVIATIONS ........................................................................................... 164 9. REFERENCES .................................................................................................. 168 " | |
| dc.language.iso | en | |
| dc.subject | Nrf2/BMP訊息傳遞 | zh_TW |
| dc.subject | 帕金森氏症 | zh_TW |
| dc.subject | 天麻 | zh_TW |
| dc.subject | 富含白胺酸重複激酶2號 | zh_TW |
| dc.subject | 膠細胞 | zh_TW |
| dc.subject | Nrf2/BMP pathway | en |
| dc.subject | Parkinson’s disease | en |
| dc.subject | Gastrodia elata Blume | en |
| dc.subject | Leucine-rich repeat kinase 2 | en |
| dc.subject | glial cell | en |
| dc.title | 天麻萃取物對於Lrrk2-G2019S帕金森氏症動物模式之效果與機制 | zh_TW |
| dc.title | The effects and mechanisms of Gastrodia elata Blume extract in Lrrk2-G2019S Parkinson's disease models | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 簡正鼎(Cheng-Ting Chien) | |
| dc.contributor.oralexamcommittee | 賴文崧(Hsin-Tsai Liu),謝淑貞(Chih-Yang Tseng),林靜嫻,林書葦 | |
| dc.subject.keyword | 帕金森氏症,天麻,富含白胺酸重複激酶2號,膠細胞,Nrf2/BMP訊息傳遞, | zh_TW |
| dc.subject.keyword | Parkinson’s disease,Gastrodia elata Blume,Leucine-rich repeat kinase 2,glial cell,Nrf2/BMP pathway, | en |
| dc.relation.page | 192 | |
| dc.identifier.doi | 10.6342/NTU202101998 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-08-04 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 食品科技研究所 | zh_TW |
| dc.date.embargo-lift | 2026-08-01 | - |
| 顯示於系所單位： | 食品科技研究所 | |
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