亨廷顿氏病的神经兴奋和线粒体毒性发病机理与动物模型  

Excitotoxicity and mitochondrial pathogenesis and animal models of Huntington’s disease

作　　者：唐文洁 黄艳 王力峰 魏佑震[1] 谢元云[3] TANG Wenjie;HUANG Yan;WANG Lifeng;WEI Youzhen;XIE Yuanyun(Research Center for Translational Medicine&Key Laboratory of Arrhythmias of the Ministry of Education of China,Shanghai East Hospital,Tongji University School of Medicine,Shanghai 200120;China.2.Rehabilitation Center,Qilu Children’s Hospital,Shandong University,Jinan 250022;.3.National Clinic and Medicine Research Institute for Geriatric Diseases,the First Affiliated Hospital,Gannan University of Medical Sciences,Ganzhou 341000)

机构地区：[1]同济大学附属东方医院转化医学研究中心,教育部心律失常重点实验室,上海200120 [2]山东大学齐鲁儿童医院康复科,济南250022 [3]赣南医学院附属第一医院国家老年病临床研究中心,江西赣州341000

出　　处：《中国实验动物学报》2021年第4期553-562,共10页Acta Laboratorium Animalis Scientia Sinica

摘　　要：亨廷顿氏病(Huntington’s disease,HD)作为一种显性遗传性神经退行疾病,表现为运动、智力、心理功能障碍。目前尚无有效的治疗或预防措施;针对各种HD症状的药物和控制措施效果不理想。1993年确认HD发病是由于HD基因(HTT)中CAG序列重复扩增超过36次或以上,翻译为突变的多聚谷氨酰胺,引起兴奋性神经毒性和线粒体能量代谢异常等,导致大脑皮质和基底核神经退行性变和功能障碍。为更全面认识HD发病机理、研究兴奋性神经毒性和线粒体能量代谢异常所致的脑组织及神经元损伤分子机制,研发相应的治疗性药物及方案,了解并掌控相应的动物模型十分重要。本文将介绍以HD组织病理学以及生物化学为发病机制而建立的HD动物模型,即兴奋性神经毒性模型和线粒体毒素模型。Huntington’s disease(HD)is an inherited autosomal dominant and progressive neurodegenerative disease with locomotor,cognitive,and psychiatric functional deficits.Currently,there is no cure for HD,and the clinical benefit is greatly limited for some treatments available for controlling HD symptoms.In 1993,it was discovered that HD is caused by a single Huntingtin gene(HTT)mutation with 36 CAG repeats and or more,which translates to a mutated polyglutamine,Resulting in neuronal excitotoxicity and abnormal mitochondrial energy metabolism,and eventually neurodegeneration in the cerebral cortex and basal nuclei.To better understand the pathogenesis mechanisms of HD and explore therapeutic interventions,it is important to create HD animal models.In this review,we will introduce HD animalmodels based on neuropathology,and explore the molecular biology of HD such as neural excitotoxicity and mitochondrial toxicity.

关 键 词：亨廷顿氏病 动物模型 神经元 线粒体 兴奋性氨基酸 

分 类 号：Q95-33[生物学—动物学]