药学学报, 2019, 54(8): 1372-1381
引用本文:
张宝月, 刘艾林, 杜冠华. 能量代谢紊乱对疾病的影响及其潜在药物靶点[J]. 药学学报, 2019, 54(8): 1372-1381.
ZHANG Bao-yue, LIU Ai-lin, DU Guan-hua. Energy metabolism disorder and diseases: from effects to potential targets[J]. Acta Pharmaceutica Sinica, 2019, 54(8): 1372-1381.

能量代谢紊乱对疾病的影响及其潜在药物靶点
张宝月, 刘艾林, 杜冠华
中国医学科学院、北京协和医学院药物研究所, 北京 100050
摘要:
营养物质利用障碍和线粒体损伤导致的细胞能量代谢紊乱与多种疾病密切相关,包括神经退行性疾病、癌症、代谢性疾病和心血管疾病等,了解能量代谢对疾病的影响将有助于加深对疾病的认识并可能通过改善能量代谢途径延缓疾病进程或者达到治愈的目的。本文主要综述了常见的能量代谢紊乱相关疾病异常的能量代谢现象,并总结了可能用于新药发现的相关靶点和机制,以及目前在研的通过改善能量代谢缓解疾病进程的新策略。
关键词:    能量代谢      新药发现      潜在靶点      神经退行性疾病      癌症      代谢性疾病      心血管疾病     
Energy metabolism disorder and diseases: from effects to potential targets
ZHANG Bao-yue, LIU Ai-lin, DU Guan-hua
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Cellular energy metabolism disorder caused by dysfunction of nutrient utilization and mitochondrial damage contributes to a variety of diseases, including neurodegenerative diseases, cancer, metabolic diseases, and cardiovascular diseases. Understanding the effects of energy metabolism on diseases will help to improve our knowledge about disease etiology and may serve to develop strategies to delay disease progress. There are many compounds developed for targeting energy metabolism disorders, such as small molecules targeting the 18 kDa transporter (TSPO) for treatment of Alzheimer's disease, glucagon-like peptide-1 analogues for treatment of Parkinson's disease, inhibitors of glucose transporter 1 (GLUT1) and lactate dehydrogenase A for treatment of tumors, the fibroblast growth factors based treatment for type 2 diabetes (T2D), selective ligands of peroxisome proliferator-activated receptor (PPAR)-β/δ for treatment of cardiovascular diseases. We review here the abnormal energy metabolism of common energy metabolism disorder-related diseases, summarize the potential targets that may be used for new drug discovery, and the strategies for alleviating the disease process by improving energy metabolism.
Key words:    energy metabolism    drug discovery    potential target    neurodegenerative disease    cancer    metabolic disease    cardiovascular disease   
收稿日期: 2019-03-09
DOI: 10.16438/j.0513-4870.2019-0161
基金项目: 国家自然科学基金资助项目(81673480);北京市自然基金资助项目(7192134);国家人口健康科学数据共享平台资源专项课题(NCMI-AGD05-201809);协和创新工程(2016-I2M-3-007);“重大新药创制”国家科技重大专项资助项目(2014ZX09507003-002).
通讯作者: 刘艾林,Tel/Fax:86-10-83150885,E-mail:liuailin@imm.ac.cn;杜冠华,Tel/Fax:86-10-63165184,E-mail:dugh@imm.ac.cn
Email: liuailin@imm.ac.cn;dugh@imm.ac.cn
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