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薰衣草治疗大鼠阿尔茨海默病的蛋白质药物靶点

Protein Drug Targets of Lavandula angustifolia on treatment of Rat Alzheimer's Disease.

作者信息

Zali Hakimeh, Zamanian-Azodi Mona, Rezaei Tavirani Mostafa, Akbar-Zadeh Baghban Alireza

机构信息

Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Pharm Res. 2015 Winter;14(1):291-302.

Abstract

Different treatment strategies of Alzheimer's disease (AD) are being studied for treating or slowing the progression of AD. Many pharmaceutically important regulation systems operate through proteins as drug targets. Here, we investigate the drug target proteins in beta-amyloid (Aβ) injected rat hippocampus treated with Lavandula angustifolia (LA) by proteomics techniques. The reported study showed that lavender extract (LE) improves the spatial performance in AD animal model by diminishing Aβ production in histopathology of hippocampus, so in this study neuroprotective proteins expressed in Aβ injected rats treated with LE were scrutinized. Rats were divided into three groups including normal, Aβ injected, and Aβ injected that was treated with LE. Protein expression profiles of hippocampus tissue were determined by two-dimensional electrophoresis (2DE) method and dysregulated proteins such as Snca, NF-L, Hspa5, Prdx2, Apoa1, and Atp5a1were identified by MALDI-TOF/TOF. KEGG pathway and gene ontology (GO) categories were used by searching DAVID Bioinformatics Resources. All detected protein spots were used to determine predictedinteractions with other proteins in STRING online database. Different isoforms of important protein, Snca that exhibited neuroprotective effects by anti-apoptotic properties were expressed. NF-L involved in the maintenance of neuronal caliber. Hspa5 likewise Prdx2 displays as anti-apoptotic protein that Prdx2 also involved in the neurotrophic effects. Apoa1 has anti-inflammatory activity and Atp5a1, produces ATP from ADP. To sum up, these proteins as potential drug targets were expressed in hippocampus in response to effective components in LA may have therapeutic properties for the treatment of AD and other neurodegenerative diseases.

摘要

针对阿尔茨海默病(AD)的不同治疗策略正在研究中,以治疗或减缓AD的进展。许多具有药学重要性的调节系统通过蛋白质作为药物靶点发挥作用。在此,我们通过蛋白质组学技术研究了用薰衣草(LA)处理的β-淀粉样蛋白(Aβ)注射大鼠海马体中的药物靶点蛋白。已报道的研究表明,薰衣草提取物(LE)通过减少海马体组织病理学中的Aβ产生来改善AD动物模型的空间性能,因此在本研究中,对用LE处理的Aβ注射大鼠中表达的神经保护蛋白进行了仔细研究。大鼠分为三组,包括正常组、Aβ注射组和用LE处理的Aβ注射组。通过二维电泳(2DE)方法测定海马体组织的蛋白质表达谱,并通过基质辅助激光解吸电离飞行时间质谱/串联飞行时间质谱(MALDI-TOF/TOF)鉴定失调蛋白,如突触核蛋白(Snca)、神经丝轻链(NF-L)、热休克蛋白A5(Hspa5)、过氧化物酶2(Prdx2)、载脂蛋白A1(Apoa1)和ATP合酶α亚基(Atp5a1)。通过搜索DAVID生物信息学资源使用京都基因与基因组百科全书(KEGG)途径和基因本体(GO)类别。所有检测到的蛋白质斑点用于在STRING在线数据库中确定与其他蛋白质的预测相互作用。表达了具有神经保护作用的重要蛋白质Snca的不同异构体,其通过抗凋亡特性发挥作用。NF-L参与维持神经元管径。Hspa5和Prdx2一样表现为抗凋亡蛋白,Prdx2也参与神经营养作用。Apoa1具有抗炎活性,而Atp5a1则利用二磷酸腺苷(ADP)产生三磷酸腺苷(ATP)。总之,这些作为潜在药物靶点的蛋白质在海马体中表达,可能是对LA中有效成分的反应,它们可能对治疗AD和其他神经退行性疾病具有治疗特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14be/4277642/c73fa3344845/ijpr-14-291-g001.jpg

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