Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, Republic of Korea.
Department of Basic Veterinary Sciences, College of Veterinary Medicine, University of the Philippines Los Baños, 4031 Los Baños, Philippines.
J Integr Neurosci. 2022 May 16;21(3):95. doi: 10.31083/j.jin2103095.
The central nervous system (CNS) is enriched in lipids; despite this, studies exploring the functional roles of lipids in the brain are still limited. Sterol regulatory element binding protein (SREBP) signaling is a transcriptomic pathway that predominantly participates in the maintenance of lipid homeostasis; however, its involvement in the CNS dysfunction is not well-established. In this study, we aimed to characterize and pinpoint specific genes of the SREBP pathway which may be implicated in neurodegenerative, neurological, and neuropsychiatric diseases.
bioinformatic analysis was performed using the open-source databases DisGeNET and MSigDB. Protein-protein interaction data were visualized and analyzed using STRING, after which GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were conducted via DAVID (Database for Annotation, Visualization and Integrated Discovery).
Several common genes were identified between the SREBP pathway and CNS disorders. In GO enrichment analysis, the most enriched biological processes included lipid, cholesterol, and steroid biosynthetic processes; the most enriched molecular functions were transcription factor-related; and the most enriched subcellular compartments revealed that the genes involved in CNS disorders were mainly associated with the enzyme complexes of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). In KEGG enrichment analysis, the most enriched pathway was the AMP-activated protein kinase (AMPK) signaling pathway, and the top-ranked genes significantly enriched under this pathway were , , , , , , , , , and .
The findings of this study strengthen the evidence linking the involvement of lipid homeostasis in CNS functions. We suggest herein the roles of downstream ACC and FASN enzymes and upstream AMPK signaling in the SREBP pathway as mechanisms underlying neurodegenerative, neurological, and neuropsychiatric CNS disorders.
中枢神经系统（CNS）富含脂质；尽管如此，探索脂质在大脑中的功能作用的研究仍然有限。固醇调节元件结合蛋白（SREBP）信号是一种主要参与维持脂质动态平衡的转录组途径；然而，其在中枢神经系统功能障碍中的作用尚未得到很好的确定。在这项研究中，我们旨在描述和确定 SREBP 途径中可能与神经退行性、神经和神经精神疾病相关的特定基因。
使用开放源代码数据库 DisGeNET 和 MSigDB 进行生物信息学分析。使用 STRING 可视化和分析蛋白质-蛋白质相互作用数据，然后通过 DAVID（数据库注释、可视化和综合发现）进行 GO（基因本体论）和 KEGG（京都基因与基因组百科全书）富集分析。
在 SREBP 途径和 CNS 疾病之间鉴定出几个常见基因。在 GO 富集分析中，最丰富的生物学过程包括脂质、胆固醇和类固醇生物合成过程；最丰富的分子功能是转录因子相关的；最丰富的亚细胞区室表明，与 CNS 疾病相关的基因主要与乙酰辅酶 A 羧化酶（ACC）和脂肪酸合酶（FASN）的酶复合物相关。在 KEGG 富集分析中，最丰富的途径是 AMP 激活蛋白激酶（AMPK）信号通路，在此途径下显著富集的前 10 个基因是、、、、、、、、和。
本研究的结果加强了脂质动态平衡参与中枢神经系统功能的证据。我们在此提出 SREBP 途径中下游 ACC 和 FASN 酶以及上游 AMPK 信号的作用，作为神经退行性、神经和神经精神 CNS 疾病的机制。
