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冠状病毒感染和神经退行性疾病之间的共享分子特征为广谱药物开发提供了靶点。

Shared molecular signatures between coronavirus infection and neurodegenerative diseases provide targets for broad-spectrum drug development.

机构信息

Internal Medicine-Neurology, The Third Hospital of Changsha, Changsha, 410015, China.

Bioinformatics Center, College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha, 410082, China.

出版信息

Sci Rep. 2023 Apr 4;13(1):5457. doi: 10.1038/s41598-023-29778-4.

Abstract

Growing evidences have suggested the association between coronavirus infection and neurodegenerative diseases. However, the molecular mechanism behind the association is complex and remains to be clarified. This study integrated human genes involved in infections of three coronaviruses including SARS-CoV-2, SARS-CoV and MERS-CoV from multi-omics data, and investigated the shared genes and molecular functions between coronavirus infection and two neurodegenerative diseases, namely Alzheimer's Disease (AD) and Parkinson's Disease (PD). Seven genes including HSP90AA1, ALDH2, CAV1, COMT, MTOR, IGF2R and HSPA1A, and several inflammation and stress response-related molecular functions such as MAPK signaling pathway, NF-kappa B signaling pathway, responses to oxidative or chemical stress were common to both coronavirus infection and neurodegenerative diseases. These genes were further found to interact with more than 20 other viruses. Finally, drugs targeting these genes were identified. The study would not only help clarify the molecular mechanism behind the association between coronavirus infection and neurodegenerative diseases, but also provide novel targets for the development of broad-spectrum drugs against both coronaviruses and neurodegenerative diseases.

摘要

越来越多的证据表明,冠状病毒感染与神经退行性疾病之间存在关联。然而,这种关联背后的分子机制很复杂,仍需阐明。本研究整合了多组学数据中涉及三种冠状病毒(包括 SARS-CoV-2、SARS-CoV 和 MERS-CoV)感染的人类基因,并研究了冠状病毒感染与两种神经退行性疾病(即阿尔茨海默病(AD)和帕金森病(PD))之间的共有基因和分子功能。七个基因包括 HSP90AA1、ALDH2、CAV1、COMT、MTOR、IGF2R 和 HSPA1A,以及几个与炎症和应激反应相关的分子功能,如 MAPK 信号通路、NF-κB 信号通路、对氧化或化学应激的反应,这两个与冠状病毒感染和神经退行性疾病都有关系。这些基因还与 20 多种其他病毒相互作用。最后,还确定了针对这些基因的药物。该研究不仅有助于阐明冠状病毒感染与神经退行性疾病之间关联的分子机制,而且还为开发针对冠状病毒和神经退行性疾病的广谱药物提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc5b/10073140/6175b3e7ce41/41598_2023_29778_Fig1_HTML.jpg

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