Candidates for drug repurposing to address the cognitive symptoms in schizophrenia.
Candidates for drug repurposing to address the cognitive symptoms in schizophrenia.
复制标题
重新调整药物用途以解决精神分裂症认知症状的候选者。
DOI：
10.1016/j.pnpbp.2022.110637
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发表时间：
2023
影响因子：
5.6
通讯作者：
Chen,Chi-Hua
中科院分区：
文献类型：
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作者：
Koch,Elise;Kauppi,Karolina;Chen,Chi-Hua
在蛋白质-蛋白质相互作用组中，我们先前已经确定了精神分裂症风险基因和认知表现相关基因之间的显著重叠。在这里，我们进一步研究了这种重叠，以确定潜在的候选药物，用于治疗精神分裂症的认知症状。我们首先从网络传播分析中定义了一个认知相关的精神分裂症相互作用组，并确定了已知靶向该网络中一种以上蛋白质的药物。此后，我们使用基因表达数据进一步选择药物，可以抵消精神分裂症相关的基因表达扰动。此外，我们将这些分析按性别分层，以确定精神分裂症认知症状的性别特异性药物治疗选择。在排除精神分裂症禁忌药物后，我们确定了12种药物再利用候选药物，其中大多数具有抗炎和神经保护作用。性别分层分析显示，在这12种药物中，4种仅在女性中确定，3种仅在男性中确定，5种在两种性别中确定。基于我们对疾病遗传学的生物信息学分析，我们提出了12种候选药物，这些药物值得进一步研究，用于治疗精神分裂症的认知症状，并建议这些症状可以通过性别特异性药物治疗方案来解决。
In the protein-protein interactome, we have previously identified a significant overlap between schizophrenia risk genes and genes associated with cognitive performance. Here, we further studied this overlap to identify potential candidate drugs for repurposing to treat the cognitive symptoms in schizophrenia. We first defined a cognition-related schizophrenia interactome from network propagation analyses, and identified drugs known to target more than one protein within this network. Thereafter, we used gene expression data to further select drugs that could counteract schizophrenia-associated gene expression perturbations. Additionally, we stratified these analyses by sex to identify sex-specific pharmacological treatment options for the cognitive symptoms in schizophrenia. After excluding drugs contraindicated in schizophrenia, we identified 12 drug repurposing candidates, most of which have anti-inflammatory and neuroprotective effects. Sex-stratified analyses showed that out of these 12 drugs, four were identified in females only, three were identified in males only, and five were identified in both sexes. Based on our bioinformatics analyses of disease genetics, we suggest 12 candidate drugs that warrant further examination for repurposing to treat the cognitive symptoms in schizophrenia, and suggest that these symptoms could be addressed by sex-specific pharmacological treatment options.