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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳韻如 | zh_TW |
dc.contributor.advisor | Yun-Ru Chen | en |
dc.contributor.author | 盧韋丞 | zh_TW |
dc.contributor.author | Wei-Cheng Lu | en |
dc.date.accessioned | 2023-09-15T16:11:09Z | - |
dc.date.available | 2023-09-16 | - |
dc.date.copyright | 2023-09-15 | - |
dc.date.issued | 2022 | - |
dc.date.submitted | 2002-01-01 | - |
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Cell Death Differ, 2020. 27(2): p. 540-555. 50. Zhu, D., et al., Irisin rescues diabetic cardiac microvascular injury via ERK1/2/Nrf2/HO-1 mediated inhibition of oxidative stress. Diabetes Res Clin Pract, 2022. 183: p. 109170. 51. Mattiasson, G., et al., Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat Med, 2003. 9(8): p. 1062-8. 52. Ramsden, D.B., et al., Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction. Brain Behav, 2012. 2(4): p. 468-78. 53. Sundstrom, E. and E.B. Samuelsson, Comparison of key steps in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in rodents. Pharmacol Toxicol, 1997. 81(5): p. 226-31. 54. Zhang, Q.S., et al., Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease. Acta Pharmacol Sin, 2017. 38(10): p. 1317-1328. 55. 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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/89671 | - |
dc.description.abstract | 神經退化性疾病是由諸多不同的原因造成了許多不同的病徵,如運動能力退化、記憶力下降、情緒與認知障礙。較廣為人知的有阿茲海默症、亨丁頓舞蹈症、帕金森氏症與肌萎縮性脊髓側索硬化症(俗稱:漸凍人症)等。目前對於各種神經退化性疾病並沒有有效的療法,而這方面的研究在世界各地仍然在不斷的在進行當中。鳶尾素是一種運動後由肌肉所分泌的激素,近期的研究指出在阿茲海默症小鼠模型中透過腺病毒載體在海馬迴上過表現鳶尾素能提升腦源性神經營養因子在 神經發育、存活及細胞凋亡中扮演重要的角色, 並有效的降低小鼠的記憶缺陷以 減緩阿茲海默症的病徵。在臨床觀察的報告中指出,運動能有效的改善帕金森氏 症病人的平衡感和行走障礙,且會降低病人跌倒的風險。依據現有的文獻推論, 造成類帕金森氏症的原因有很多種,但幾乎都與神經細胞粒線體的損傷有關。在 此,我想探討鳶尾素在阿茲海默症與帕金森氏症中所扮演的角色。我首先純化了 重組鳶尾素來進行研究,並進行一些改造來試圖加強鳶尾素的功能,並測試它的 構型與穩定性。在帕金森氏症的研究中,我使用 Methyl-4-phenylpyridinium iodide (MPP+) 作為創立帕金森氏症模型的工具,MPP+是一種針對多巴胺神經元的毒素, 會破壞細胞的粒線體功能並使細胞內的氧化壓力上升。結果顯示提前給予神經母 細胞瘤 SH-SY5Y 鳶尾素再給予 MPP+,能提升細胞的存活率,腹腔注射鳶尾素的 小鼠實驗的結果顯示鳶尾素能保護腦部黑質中的多巴胺分泌細胞不受 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP)的影響。在基因表現研究中,12 及 24 小 時的鳶尾素處理能顯著性的提升大鼠原代神經細胞中的 BDNF mRNA 表現量。 RNA-seq 的分析結果顯示,鳶尾素能提升肌肉收縮及生肉生存等相關基因的表現, 可能與帕金森氏症、漸凍人症治療會有些關係。本研究開創了鳶尾素在神經退化 疾病的潛能,相關實驗未來仍會持續發展。 | zh_TW |
dc.description.abstract | Neurodegenerative disorders encompass a wide range of symptoms that result from progressive damage to cells and nervous systems that are essential for mobility, coordination, strength, sensation, and cognition. The disorders include Alzheimer’s disease (AD), Huntington’s disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and many others. So far, there is still no cure for most neurodegenerative diseases. Irisin is a myokine induced after exercises. Recently, researches have demonstrated that overexpressing Irisin by adenovirus up-regulated brain-derived neurotrophic factor (BDNF) in the hippocampus and rescued the memory defect of an AD mouse model. BDNF has been reported to have important role in neuron development, survival, and apoptosis. Clinical observations for PD strongly suggest that exercise reduces gait and balance impairments as well as fall risk in the patients. Oxidative damage was suggested as a common pathway in the pathogenesis of PD-like disorders. Based on the previous literature and clinical observation, in this study, I would like to investigate the role of Irisin in PD and AD. Recombinant Irisin was expressed and purified. The conformation and stability were examined. Then, I used 1-Methyl-4-phenylpyridinium iodide (MPP+), a mitochondria toxin to dopaminergic neurons, to establish a cellular model of PD. MPP+, a dopaminergic selective neurotoxin, induces mitochondrial dysfunction and raises the level of Reactive Oxygen Species (ROS) in cell. The results doi:10.6342/NTU202203781 iv showed that pre-treatment of Irisin protected human neuroblastoma SH-SY5Y against MPP+. Intraperial injection of Irisin to mice study indicated that Irisin can rescue tyrosine hydroxylase (TH+) cell loss in substantia nigra of PD mice. Secondly, I showed that the BDNF mRNA expression level is up-regulated after 12 and 24 hr treatment of recombinant Irisin in rat primary neuron culture and Irisin may increase the expression level of BDNF protein. RNA-seq data revealed the linkage between Irisin and PD, amyotrophic lateral sclerosis (ALS). Overall, this study unleash the potential of Irisin in neurodegenerative diseases. Related experiments will be continued in the future. | en |
dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-09-15T16:11:09Z No. of bitstreams: 0 | en |
dc.description.provenance | Made available in DSpace on 2023-09-15T16:11:09Z (GMT). No. of bitstreams: 0 | en |
dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii List of figures viii Chapter 1 Introduction 1 1.1 Neurodegenerative diseases 1 1.2 Parkinson’s disease 1 1.2.1 Overview 1 1.2.2 Pathologies of Parkinson’s disease 2 1.2.3 Medical treatment of Parkinson’s disease 4 1.3 Alzheimer’s disease 5 1.3.1 Overview 5 1.4 Irisin 5 1.4.1 Physiological function of Irisin 5 1.4.2 The Structural overview of Irisin 6 1.4.3 The role of Irisin in neurodegenerative diseases 7 1.5 Research aim 8 Chapter 2 Methods 10 2.1Methods 10 2.1.1 Protein expression and purification 10 2.1.2 Cross-linking of Irisin 11 2.1.3 Circular dichroism spectrum 12 2.1.4 Intrinsic fluorescence spectrum 12 2.1.5 Absorbance spectrum 12 2.1.6 Isolation of primary cortical neurons from E17 rat 13 2.1.7 Cell toxicity assay 13 2.1.8 Real-time quantitative PCR (RT-qPCR) 14 2.1.9 Mito stress test 14 2.1.10 Modeling of the experimental animals and medication 15 2.1.11 Rotarod test 16 2.1.12 Open field test 16 2.1.13 Immunohistochemical staining of Tyrosine Hydroxylase 17 2.1.14 RNA-sequencing 18 2.1.15 Western blotting 18 Chapter 3 Results 19 3.1 Purification of Irisin. 19 3.2 Circular dichroism spectra of Irisin and cross-linked Irisin show a more stable secondary structure in cross-linked Irisin. 20 3.3 Irisin reduces cell death caused by MPP+. 21 3.4 Irisin up-regulates UCP5 and BDNF in vitro. 21 3.5 Seahorse mito stress assay shows an increase of spare capacity after 72 hr of Irisin treatment. 23 3.6 Irisin reduces the compensative effect after MPTP injection in mice behavioral test. 24 3.7 TH+ cell number loss is rescued in substantia nigra of PD mice with pre-injection of Irisin. 25 Chapter 4 Discussion 27 Reference 54 Appendix 58 Materials 58 Culture medium 60 Reagent 61 Primer for RT-qPCR 62 | - |
dc.language.iso | en | - |
dc.title | 探討鳶尾素在神經退化性疾病中的效果 | zh_TW |
dc.title | Investigating the effect of Irisin in neurodegenerative diseases | en |
dc.type | Thesis | - |
dc.date.schoolyear | 110-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.coadvisor | 黃楓婷 | zh_TW |
dc.contributor.coadvisor | Feng-Ting Huang | en |
dc.contributor.oralexamcommittee | 張世宗 | zh_TW |
dc.contributor.oralexamcommittee | Shih-Chung Chang | en |
dc.subject.keyword | 神經退化性疾病,帕金森氏症,鳶尾素,粒線體, | zh_TW |
dc.subject.keyword | Neurodegenerative diseases,PD,Irisin,mitochondria, | en |
dc.relation.page | 64 | - |
dc.identifier.doi | 10.6342/NTU202203781 | - |
dc.rights.note | 同意授權(全球公開) | - |
dc.date.accepted | 2022-09-25 | - |
dc.contributor.author-college | 生命科學院 | - |
dc.contributor.author-dept | 生化科技學系 | - |
顯示於系所單位: | 生化科技學系 |
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