Nguyen Thanh-Phuong, Priami Corrado, Caberlotto Laura
1] The Microsoft Research, University of Trento Centre for Computational Systems Biology (COSBI), Piazza Manifattura 1, 38068, Rovereto, Italy [2] Life Sciences Research Unit, University of Luxembourg, 162 A, avenue de la Faïencerie, L-1511 Luxembourg.
1] The Microsoft Research, University of Trento Centre for Computational Systems Biology (COSBI), Piazza Manifattura 1, 38068, Rovereto, Italy [2] Department of Mathematics, University of Trento, Via Sommarive, 14-38123 Povo, Italy.
Sci Rep. 2015 Jul 8;5:11104. doi: 10.1038/srep11104.
Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia.
痴呆症是一种大脑神经退行性疾病,其认知和心理功能会逐渐且永久性丧失。尽管全球痴呆症患者数量在稳步增加,且该疾病的分子特征研究也取得了进展,但目前针对痴呆症的医学治疗纯粹只是对症治疗,效果甚微。我们提出了一种新颖的多关系关联挖掘方法,该方法整合了近年来积累的大量科学数据,以预测痴呆症创新治疗的潜在新靶点。由于能够处理大量异构数据,我们的方法具有高性能,并预测了众多药物靶点,包括几种丝氨酸苏氨酸激酶和一种G蛋白偶联受体。预测的药物靶点主要在功能上与代谢、细胞表面受体信号通路、免疫反应、细胞凋亡和长期记忆相关。在高度代表性的激酶家族和G蛋白偶联受体中,DLG4(PSD - 95)和缓激肽受体2也因其在记忆和认知中的作用而受到关注,如先前研究中所述。这些新的假定靶点为开发治疗痴呆症的新型治疗方法带来了希望。