Zhang Jingyi, Tsui Ka Chun, Lee Hoi Ying, Aquili Luca, Wong Kah Hui, Kocabicak Ersoy, Temel Yasin, Lu Zhiliang, Fung Man-Lung, Kalueff Allan, Lim Lee Wei
Department of Biosciences and Bioinformatics, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China.
Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China.
Int J Mol Sci. 2025 Jan 2;26(1):338. doi: 10.3390/ijms26010338.
Melatonin is a hormone released by the pineal gland that regulates the sleep-wake cycle. It has been widely studied for its therapeutic effects on Alzheimer's disease (AD), particularly through the amyloidosis, oxidative stress, and neuroinflammation pathways. Nevertheless, the mechanisms through which it exerts its neuroprotective effects in AD are still largely unknown. Data mining was used to identify potential gene targets that link melatonin's effects to AD pathways, yielding a comprehensive view of the underlying molecular mechanisms. We identified 3397 genes related to AD from DisGeNet and 329 melatonin gene targets from ChEMBL, which revealed 223 overlapping genes and the potential shared pathways. These genes were used to construct a protein-protein interaction (PPI) network comprising 143 nodes and 823 edges, which demonstrated significant PPI enrichment. A cluster analysis highlighted two key clusters centered on and , with both genes playing crucial roles in steroid hormone signaling, apoptosis, and monoamine neurotransmission. Gene Ontology (GO) enrichment and KEGG pathway analyses further elucidated their involvement in critical pathways, for instance, steroid hormone signaling and apoptosis regulation, significantly influencing AD pathology through mechanisms such as extracellular matrix remodeling, epigenetic modifications, and neuroinflammation. Our findings emphasize and as important gene targets for future research on melatonin treatment in AD, paving the way for further investigations into their roles in AD pathophysiology.
褪黑素是一种由松果体释放的激素,它调节睡眠-觉醒周期。它因其对阿尔茨海默病(AD)的治疗作用而被广泛研究,特别是通过淀粉样变性、氧化应激和神经炎症途径。然而,它在AD中发挥神经保护作用的机制仍然很大程度上未知。数据挖掘被用于识别将褪黑素的作用与AD途径联系起来的潜在基因靶点,从而对潜在的分子机制有一个全面的了解。我们从DisGeNet中鉴定出3397个与AD相关的基因,从ChEMBL中鉴定出329个褪黑素基因靶点,这揭示了223个重叠基因和潜在的共享途径。这些基因被用于构建一个包含143个节点和823条边的蛋白质-蛋白质相互作用(PPI)网络,该网络显示出显著的PPI富集。聚类分析突出了以 和 为中心的两个关键聚类,这两个基因在类固醇激素信号传导、细胞凋亡和单胺神经传递中都起着关键作用。基因本体(GO)富集和KEGG途径分析进一步阐明了它们参与关键途径,例如类固醇激素信号传导和细胞凋亡调节,通过细胞外基质重塑、表观遗传修饰和神经炎症等机制显著影响AD病理学。我们的发现强调 和 作为未来AD褪黑素治疗研究的重要基因靶点,为进一步研究它们在AD病理生理学中的作用铺平了道路。