Department of Computer Science and Engineering, Amrita School of Computing, Amrita Vishwa Vidyapeetham, Chennai 641112, India.
Department of Sciences, Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Chennai 601103, India.
Genes (Basel). 2024 May 11;15(5):614. doi: 10.3390/genes15050614.
Alzheimer's disease (AD), a multifactorial neurodegenerative disorder, is prevalent among the elderly population. It is a complex trait with mutations in multiple genes. Although the US Food and Drug Administration (FDA) has approved a few drugs for AD treatment, a definitive cure remains elusive. Research efforts persist in seeking improved treatment options for AD. Here, a hybrid pipeline is proposed to apply text mining to identify comorbid diseases for AD and an omics approach to identify the common genes between AD and five comorbid diseases-dementia, type 2 diabetes, hypertension, Parkinson's disease, and Down syndrome. We further identified the pathways and drugs for common genes. The rationale behind this approach is rooted in the fact that elderly individuals often receive multiple medications for various comorbid diseases, and an insight into the genes that are common to comorbid diseases may enhance treatment strategies. We identified seven common genes-, , , , , , and -for AD and five comorbid diseases. We investigated the drugs interacting with these common genes using LINCS gene-drug perturbation. Our analysis unveiled several promising candidates, including MG-132 and Masitinib, which exhibit potential efficacy for both AD and its comorbid diseases. The pipeline can be extended to other diseases.
阿尔茨海默病（AD）是一种多因素神经退行性疾病，在老年人群中较为普遍。它是一种具有多种基因突变的复杂特征。尽管美国食品和药物管理局（FDA）已经批准了几种用于 AD 治疗的药物，但仍未找到明确的治愈方法。研究人员仍在努力寻找改善 AD 治疗的方法。在这里，我们提出了一个混合管道，应用文本挖掘来识别 AD 的共病，以及一种组学方法来识别 AD 和五种共病（痴呆、2 型糖尿病、高血压、帕金森病和唐氏综合征）之间的共同基因。我们进一步确定了共同基因的途径和药物。这种方法的基本原理是，老年人经常因各种共病而服用多种药物，对共病共同的基因有深入了解可能会增强治疗策略。我们确定了七个 AD 和五种共病的共同基因，、、、、、和。我们使用 LINCS 基因-药物扰动研究了与这些共同基因相互作用的药物。我们的分析揭示了几个有前途的候选药物，包括 MG-132 和 Masitinib，它们对 AD 和其共病都有潜在的疗效。该管道可以扩展到其他疾病。
