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藏红花改善了帕金森病果蝇模型的运动症状、缩短寿命和视网膜变性。

Saffron ameliorated motor symptoms, short life span and retinal degeneration in Parkinson's disease fly models.

机构信息

Tokyo Research Center, Kyushin Pharmaceutical Co, Ltd., Suginami 166-0012, Tokyo, Japan; Institute for Chronobiology, Foundation for Advancement of International Science (FAIS), Tsukuba, 305-0821 Ibaraki, Japan.

Institute for Chronobiology, Foundation for Advancement of International Science (FAIS), Tsukuba, 305-0821 Ibaraki, Japan.

出版信息

Gene. 2021 Oct 5;799:145811. doi: 10.1016/j.gene.2021.145811. Epub 2021 Jul 2.

DOI:10.1016/j.gene.2021.145811
PMID:34224829
Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the brain. α-Synuclein is an aggregation-prone neural protein that plays a role in the pathogenesis of PD. In our previous paper, we found that saffron; the stigma of Crocus sativus Linné (Iridaceae), and its constituents (crocin and crocetin) suppressed aggregation of α-synuclein and promoted the dissociation of α-synuclein fibrils in vitro. In this study, we investigated the effect of dietary saffron and its constituent, crocetin, in vivo on a fly PD model overexpressing several mutant α-synuclein in a tissue-specific manner. Saffron and crocetin significantly suppressed the decrease of climbing ability in the Drosophila overexpressing A30P (A30P fly PD model) or G51D (G51D fly PD model) mutated α-synuclein in neurons. Saffron and crocetin extended the life span in the G51D fly PD model. Saffron suppressed the rough-eyed phenotype and the dispersion of the size histogram of the ocular long axis in the eye of A30P fly PD model. Saffron had a cytoprotective effect on a human neuronal cell line with α-synuclein fibrils. These data showed that saffron and its constituent crocetin have protective effects on the progression of PD disease in animals in vivo and suggest that saffron and crocetin can be used to treat PD.

摘要

帕金森病(PD)是一种常见的神经退行性疾病,其运动症状与大脑中多巴胺能神经元的丧失有关。α-突触核蛋白是一种易于聚集的神经蛋白,在 PD 的发病机制中起作用。在我们之前的论文中,我们发现藏红花;藏红花 Crocus sativus Linné(鸢尾科)的柱头及其成分(藏红花酸和西红花酸)抑制α-突触核蛋白的聚集,并促进α-突触核蛋白纤维的解离在体外。在这项研究中,我们研究了饮食藏红花及其成分西红花酸在体内对几种突变α-突触核蛋白在组织特异性方式下过度表达的果蝇 PD 模型的影响。藏红花和西红花显著抑制了神经元中过度表达 A30P(A30P 果蝇 PD 模型)或 G51D(G51D 果蝇 PD 模型)突变α-突触核蛋白的果蝇攀爬能力下降。藏红花延长了 G51D 果蝇 PD 模型的寿命。藏红花抑制了 A30P 果蝇 PD 模型的眼睛中粗眼表型和眼长轴大小分布直方图的离散。藏红花对携带α-突触核蛋白纤维的人神经元细胞系具有细胞保护作用。这些数据表明,藏红花及其成分西红花对体内动物 PD 疾病的进展具有保护作用,并表明藏红花和西红花可用于治疗 PD。

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Saffron ameliorated motor symptoms, short life span and retinal degeneration in Parkinson's disease fly models.藏红花改善了帕金森病果蝇模型的运动症状、缩短寿命和视网膜变性。
Gene. 2021 Oct 5;799:145811. doi: 10.1016/j.gene.2021.145811. Epub 2021 Jul 2.
2
Effects of saffron and its constituents, crocin-1, crocin-2, and crocetin on α-synuclein fibrils.藏红花及其成分藏红花素-1、藏红花素-2和藏红花酸对α-突触核蛋白原纤维的影响。
J Nat Med. 2018 Jan;72(1):274-279. doi: 10.1007/s11418-017-1150-1. Epub 2017 Nov 17.
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Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of parkinsonism.藏红花和藏红花素在帕金森病果蝇模型中的神经保护作用证据。
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Intestinal formation of trans-crocetin from saffron extract (Crocus sativus L.) and in vitro permeation through intestinal and blood brain barrier.藏红花提取物(番红花)中反式藏花酸的肠道形成及体外透过肠道和血脑屏障的研究
Phytomedicine. 2015 Jan 15;22(1):36-44. doi: 10.1016/j.phymed.2014.10.009. Epub 2014 Nov 11.
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A stress-enhanced model for discovery of disease-modifying gene: Ece1-suppresses the toxicity of α-synuclein A30P.增强应激模型发现疾病修饰基因:Ece1 抑制α-突触核蛋白 A30P 的毒性。
Neurobiol Dis. 2018 Jun;114:153-163. doi: 10.1016/j.nbd.2018.03.003. Epub 2018 Mar 7.
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Mutant alpha-synuclein-induced degeneration is reduced by parkin in a fly model of Parkinson's disease.在帕金森病果蝇模型中,帕金蛋白可减轻突变型α-突触核蛋白诱导的变性。
Genome. 2006 May;49(5):505-10. doi: 10.1139/g06-011.
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Olfactory deficits in an alpha-synuclein fly model of Parkinson's disease.帕金森病α-突触核蛋白果蝇模型中的嗅觉缺陷
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Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo.藏红花中类胡萝卜素对体外和体内神经元损伤的保护作用。
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Parkin counteracts symptoms in a Drosophila model of Parkinson's disease.帕金蛋白可缓解帕金森病果蝇模型中的症状。
BMC Neurosci. 2004 Apr 16;5:14. doi: 10.1186/1471-2202-5-14.
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E46K mutant α-synuclein is more degradation resistant and exhibits greater toxic effects than wild-type α-synuclein in Drosophila models of Parkinson's disease.E46K 突变型 α-突触核蛋白比野生型 α-突触核蛋白在帕金森病的果蝇模型中更具降解抗性,并表现出更大的毒性作用。
PLoS One. 2019 Jun 26;14(6):e0218261. doi: 10.1371/journal.pone.0218261. eCollection 2019.

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