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提取物对帕金森病细胞系统模型的治疗作用。

Therapeutic Effect of Extract on a Cell System Model for Parkinson's Disease.

作者信息

Ho Dong Hwan, Kim Hyejung, Nam Daleum, Seo Mi Kyoung, Park Sung Woo, Kim Dong-Kyu, Son Ilhong

机构信息

InAm Neuroscience Research Center, Sanbon Medical Center, College of Medicine, Wonkwang University, 321, Sanbon-ro, Gunpo-si 15865, Republic of Korea;

Paik Institute for Clinical Research, Inje University College of Medicine, Busan-si 47392, Republic of Korea;

出版信息

NeuroSci. 2024 Aug 30;5(3):301-314. doi: 10.3390/neurosci5030024. eCollection 2024 Sep.

DOI:10.3390/neurosci5030024
PMID:39483283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11469749/
Abstract

Leucine-rich repeat kinase 2 (LRRK2) and α-synuclein are involved in the pathogenesis of Parkinson's disease. The activity of LRRK2 in microglial cells is associated with neuroinflammation, and LRRK2 inhibitors are crucial for alleviating this neuroinflammatory response. α-synuclein contributes to oxidative stress in the dopaminergic neuron and neuroinflammation through Toll-like receptors in microglia. In this study, we investigated the effect of the marine alga on neuroinflammation by examining LRRK2 activation and the aggregation of α-synuclein. extract inhibits LRRK2 activity in vitro and decreases lipopolysaccharide (LPS)-induced LRRK2 upregulation in BV2, a mouse microglial cell line. Treatment with extract decreased tumor necrosis factor-α (TNF-α) gene expression by LPS through LRRK2 inhibition in BV2. It also attenuated TNF-α gene expression, inducible nitric oxide synthase, and the release of TNF-α and cellular nitric oxide in rat primary microglia. Furthermore, extract prevented rotenone (RTN)-induced oxidative stress in primary rat astrocytes and inhibited α-synuclein fibrilization in an in vitro assay using recombinant α-synuclein and in the differentiated human dopaminergic neuronal cell line SH-SY5Y (dSH). The extract increased lysosomal activity in dSH cells. In addition, extract slightly prolonged the lifespan of , which was reduced by RTN treatment.

摘要

富含亮氨酸重复激酶2(LRRK2)和α-突触核蛋白参与帕金森病的发病机制。小胶质细胞中LRRK2的活性与神经炎症相关,LRRK2抑制剂对于减轻这种神经炎症反应至关重要。α-突触核蛋白通过小胶质细胞中的Toll样受体导致多巴胺能神经元的氧化应激和神经炎症。在本研究中,我们通过检测LRRK2激活和α-突触核蛋白聚集来研究海藻对神经炎症的影响。海藻提取物在体外抑制LRRK2活性,并降低脂多糖(LPS)诱导的小鼠小胶质细胞系BV2中LRRK2的上调。用海藻提取物处理通过抑制BV2中的LRRK2降低了LPS诱导的肿瘤坏死因子-α(TNF-α)基因表达。它还减弱了大鼠原代小胶质细胞中TNF-α基因表达、诱导型一氧化氮合酶以及TNF-α和细胞一氧化氮的释放。此外,海藻提取物在原代大鼠星形胶质细胞中预防了鱼藤酮(RTN)诱导的氧化应激,并在使用重组α-突触核蛋白的体外试验以及分化的人多巴胺能神经元细胞系SH-SY5Y(dSH)中抑制了α-突触核蛋白纤维化。该提取物增加了dSH细胞中的溶酶体活性。此外,海藻提取物略微延长了经RTN处理后缩短的线虫寿命。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/a50a4e910017/neurosci-05-00024-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/ef68992bd095/neurosci-05-00024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/5e88c50c8e62/neurosci-05-00024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/9b1ce8774a73/neurosci-05-00024-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/d664cb0353cd/neurosci-05-00024-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/1233712d94f6/neurosci-05-00024-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/cd281bd7a94b/neurosci-05-00024-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/a50a4e910017/neurosci-05-00024-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/ef68992bd095/neurosci-05-00024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/5e88c50c8e62/neurosci-05-00024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/9b1ce8774a73/neurosci-05-00024-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/d664cb0353cd/neurosci-05-00024-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/1233712d94f6/neurosci-05-00024-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/cd281bd7a94b/neurosci-05-00024-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9951/11469749/a50a4e910017/neurosci-05-00024-g007.jpg

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本文引用的文献

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Discovery of small molecule benzothiazole and indole derivatives tackling tau 2N4R and α-synuclein fibrils.发现小分子苯并噻唑和吲哚衍生物可解决 Tau 2N4R 和 α-突触核蛋白纤维。
Bioorg Med Chem. 2024 Feb 15;100:117613. doi: 10.1016/j.bmc.2024.117613. Epub 2024 Jan 28.
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Glial senescence enhances α-synuclein pathology owing to its insufficient clearance caused by autophagy dysfunction.由于自噬功能障碍导致清除不足,神经胶质细胞衰老会加剧α-突触核蛋白病变。
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The role of microglial LRRK2 kinase in manganese-induced inflammatory neurotoxicity via NLRP3 inflammasome and RAB10-mediated autophagy dysfunction.
小胶质细胞 LRRK2 激酶通过 NLRP3 炎性体和 RAB10 介导的自噬功能障碍在锰诱导的炎症性神经毒性中的作用。
J Biol Chem. 2023 Jul;299(7):104879. doi: 10.1016/j.jbc.2023.104879. Epub 2023 Jun 1.
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LRRK2 Kinase Inhibition Attenuates Astrocytic Activation in Response to Amyloid β Fibrils.LRRK2 激酶抑制可减轻淀粉样β纤维对星形胶质细胞的激活。
Biomolecules. 2023 Feb 6;13(2):307. doi: 10.3390/biom13020307.
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The antagonistic activity of extracts on mPRα.提取物对 mPRα 的拮抗活性。
Nat Prod Res. 2023 Jun;37(11):1872-1876. doi: 10.1080/14786419.2022.2120873. Epub 2022 Sep 6.
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LRRK2 Inhibition Mitigates the Neuroinflammation Caused by TLR2-Specific α-Synuclein and Alleviates Neuroinflammation-Derived Dopaminergic Neuronal Loss.LRRK2 抑制减轻了 TLR2 特异性 α-突触核蛋白引起的神经炎症,并缓解了神经炎症引起的多巴胺能神经元丢失。
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7
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