研究生: |
瑋 克 Kolas, Viktoryia |
---|---|
論文名稱: |
P5及其合成衍生物透過CLIP1重組細胞骨架以促進神經發育 Pregnenolone and its non-metabolized derivatives reorganize cytoskeleton to promote neuronal development via CLIP1 |
指導教授: |
鍾邦柱
Chung, Bon-chu |
口試委員: |
江運金
Jiang, Yun-Jin 喻秋華 Yuh, Chiou-Hwa 林玉俊 Lin, Yu-Chun 王歐力 Wagner, Oliver I. |
學位類別: |
博士 Doctor |
系所名稱: |
生命科學暨醫學院 - 分子與細胞生物研究所 Institute of Molecular and Cellular Biology |
論文出版年: | 2023 |
畢業學年度: | 111 |
語文別: | 英文 |
論文頁數: | 101 |
中文關鍵詞: | 孕烯醇酮 、CLIP1 、細胞骨架 |
外文關鍵詞: | pregnenolone, CLIP1, cytoskeleton |
相關次數: | 點閱:2 下載:0 |
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孕烯醇酮(P5)是所有類固醇的前體,在性腺、腎上腺和大腦中產生。P5可以改善認知功能並減輕精神分裂症的壓力和負性癥狀。P5控制斑馬魚的胚胎細胞遷移。由P5活化的CLIP1 (CLIP-170) 可以加速微管的聚合。CLIP1是一種微管+TIP蛋白,可促進神經元的極化和F-肌動蛋白的延長。
P5和CLIP1協同調節斑馬魚胚胎中的外包運動。本篇論文研究了依賴P5激活的CLIP1對神經元和大腦發育的作用。依賴P5激活的CLIP1影響微管蛋白PTM在發育軸突中的平衡,促進微管-肌動蛋白的交互作用,進而造成神經突和軸突生長,軸突加速特化和大腦的早期發育。
P5-CLIP1作用機制在斑馬魚和小鼠之間是保守的。P5及其不可代謝衍生物以濃度依賴性方式作用,並在不同的神經元中產生相似的效果。P5及其不可代謝衍生物為神經發育和神經退行性疾病的擬議藥物。目前的結果描述了P5神經類固醇功能的基本機制之一是它能夠通過CLIP1重組發育神經元中的細胞骨架。
Pregnenolone (P5) is a precursor of all steroids, that is produced in gonads, adrenal glands and brain. P5 improves cognitive functions, reduces stress and negative symptoms of schizophrenia. P5 is required for embryonic cell movement in zebrafish. CLIP1(CLIP-170) activated by P5 accelerates microtubule polymerization.
CLIP1 is a microtubule +TIP protein, that promotes neuronal polarization, affects dendrites morphology and cell migration. P5 and CLIP1 synergistically regulate epiboly movement in zebrafish embryos. This thesis examines the role of P5-dependent CLIP1 activation on neurons and brain development.
The mechanism of P5-dependent CLIP1 activation affects the balance of tubulin post translational modification (PTM) in developing axon, promotes microtubule-actin crosstalk resulting in increased neurites and axon outgrowth, acceleration of axon specification and early stages of brain development. P5-CLIP1 mechanism is conservative between zebrafish and mice. P5 and its non-metabolized derivatives work in concentration-dependent manner and demonstrate similar effects in different neurons. P5 and its non-metabolized derivatives are proposed drugs for neurodevelopmental and neurodegenerative diseases. Current results characterize one of the basic mechanisms of P5 neurosteroidal function which relies on P5’s ability to reorganize the cytoskeleton in developing neurons via CLIP1.
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