Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects.
Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects.
复制标题
全转录组计算机筛选表明心血管和传染病与非典型抗精神病药物副作用的作用机制有关。
DOI：
10.1002/trc2.12078
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Malekizadeh Y
中科院分区：
文献类型：
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作者：
Malekizadeh Y
背景抗精神病药物可显著增加痴呆患者的卒中/血栓栓塞事件、感染和死亡，但对它们为何有害却知之甚少。使用一种新的应用程序的药物再利用的范例，我们的目的是确定潜在的机制，潜在的不良事件。MethodsWhole transcriptome签名产生与氨磺必利，利培酮和volinanserin使用RNA测序处理的SH‐ SY 5 Y细胞。进行生物信息学分析，从国家生物技术信息中心基因表达综合库（NCBI GEO）repositions. ResultsAtheropathy，静脉血栓栓塞和流感NCBI GEO-衍生的样品抗精神病药物的签名和表达数据之间的关联得分积极对抗抗精神病药物的签名。富含抗精神病药物特征的途径与心血管和免疫系统有关（例如，脑源性神经营养因子[BDNF]、血小板源性生长因子受体[PDGFR]-β、肿瘤坏死因子[TNF]、转化生长因子[TGF]-β、硒氨基酸代谢，（流感感染）结论这些发现首次将抗精神病药物与特定的心血管和感染性疾病联系起来，这些疾病是已知的副作用他们在痴呆症中的使用，提供新的信息来解释相关的不良事件。
BackgroundStroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events.MethodsWhole transcriptome signatures were generated for SH‐SY5Y cells treated with amisulpride, risperidone, and volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository.ResultsAtherosclerosis, venous thromboembolism, and influenza NCBI GEO‐derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]‐beta, tumor necrosis factor [TNF], transforming growth factor [TGF]‐beta, selenoamino acid metabolism, and influenza infection).ConclusionsThese findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.