{"title":"亨廷顿氏病的代谢失调:神经元和神经胶质的视角。","authors":"","doi":"10.1016/j.nbd.2024.106672","DOIUrl":null,"url":null,"abstract":"<div><div>Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutant huntingtin protein with an abnormal CAG/polyQ expansion in the N-terminus of HTT exon 1. HD is characterized by progressive neurodegeneration and metabolic abnormalities, particularly in the brain, which accounts for approximately 20 % of the body's resting metabolic rate. Dysregulation of energy homeostasis in HD includes impaired glucose transporters, abnormal functions of glycolytic enzymes, changes in tricarboxylic acid (TCA) cycle activity and enzyme expression in the basal ganglia and cortical regions of both HD mouse models and HD patients. However, current understanding of brain cell behavior during energy dysregulation and its impact on neuron–glia crosstalk in HD remains limited. This review provides a comprehensive summary of the current understanding of the differences in glucose metabolism between neurons and glial cells in HD and how these differences contribute to disease development compared with normal conditions. We also discuss the potential impact of metabolic shifts on neuron–glia communication in HD. A deeper understanding of these metabolic alterations may reveal potential therapeutic targets for future drug development.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Metabolic dysregulation in Huntington's disease: Neuronal and glial perspectives\",\"authors\":\"\",\"doi\":\"10.1016/j.nbd.2024.106672\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutant huntingtin protein with an abnormal CAG/polyQ expansion in the N-terminus of HTT exon 1. HD is characterized by progressive neurodegeneration and metabolic abnormalities, particularly in the brain, which accounts for approximately 20 % of the body's resting metabolic rate. Dysregulation of energy homeostasis in HD includes impaired glucose transporters, abnormal functions of glycolytic enzymes, changes in tricarboxylic acid (TCA) cycle activity and enzyme expression in the basal ganglia and cortical regions of both HD mouse models and HD patients. However, current understanding of brain cell behavior during energy dysregulation and its impact on neuron–glia crosstalk in HD remains limited. This review provides a comprehensive summary of the current understanding of the differences in glucose metabolism between neurons and glial cells in HD and how these differences contribute to disease development compared with normal conditions. We also discuss the potential impact of metabolic shifts on neuron–glia communication in HD. A deeper understanding of these metabolic alterations may reveal potential therapeutic targets for future drug development.</div></div>\",\"PeriodicalId\":19097,\"journal\":{\"name\":\"Neurobiology of Disease\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurobiology of Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0969996124002729\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969996124002729","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
亨廷顿氏病(Huntington's disease,HD)是一种常染色体显性神经退行性疾病,由 HTT 第 1 外显子 N 端异常 CAG/polyQ 扩增的突变亨廷丁蛋白引起。HD 的特征是进行性神经变性和代谢异常,尤其是在大脑中,大脑的代谢率约占人体静息代谢率的 20%。HD 能量平衡失调包括葡萄糖转运体受损、糖酵解酶功能异常、三羧酸(TCA)循环活性变化以及 HD 小鼠模型和 HD 患者基底节和皮质区域的酶表达。然而,目前对能量失调时脑细胞行为及其对 HD 神经元-神经胶质细胞串扰影响的了解仍然有限。本综述全面总结了目前对 HD 神经元和神经胶质细胞之间葡萄糖代谢差异的理解,以及与正常情况相比,这些差异是如何导致疾病发展的。我们还讨论了新陈代谢变化对 HD 中神经元-神经胶质沟通的潜在影响。更深入地了解这些代谢变化可能会为未来的药物开发揭示潜在的治疗目标。
Metabolic dysregulation in Huntington's disease: Neuronal and glial perspectives
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutant huntingtin protein with an abnormal CAG/polyQ expansion in the N-terminus of HTT exon 1. HD is characterized by progressive neurodegeneration and metabolic abnormalities, particularly in the brain, which accounts for approximately 20 % of the body's resting metabolic rate. Dysregulation of energy homeostasis in HD includes impaired glucose transporters, abnormal functions of glycolytic enzymes, changes in tricarboxylic acid (TCA) cycle activity and enzyme expression in the basal ganglia and cortical regions of both HD mouse models and HD patients. However, current understanding of brain cell behavior during energy dysregulation and its impact on neuron–glia crosstalk in HD remains limited. This review provides a comprehensive summary of the current understanding of the differences in glucose metabolism between neurons and glial cells in HD and how these differences contribute to disease development compared with normal conditions. We also discuss the potential impact of metabolic shifts on neuron–glia communication in HD. A deeper understanding of these metabolic alterations may reveal potential therapeutic targets for future drug development.
期刊介绍:
Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.