{"title":"阿尔茨海默病中的线粒体转运蛋白(TSPO):治疗和免疫调节功能。","authors":"","doi":"10.1016/j.biochi.2024.07.003","DOIUrl":null,"url":null,"abstract":"<div><p>The translocator protein (TSPO) has been widely investigated as a PET-imaging biomarker of neuroinflammation and, more recently, as a therapeutic target for the treatment of neurodegenerative disease. TSPO ligands have been shown to exert neuroprotective effects in vivo and <em>in vitro</em> models of Alzheimer's disease (AD), by reducing toxic beta amyloid peptides, and attenuating brain atrophy. Recent transcriptomic and proteomic analyses, and the generation of TSPO-KO mice, have enabled new insights into the mechanistic function of TSPO in AD. Using a multi-omics approach in both TSPO-KO- and TSPO ligand-treated mice, we have demonstrated a key role for TSPO in microglial respiratory metabolism and phagocytosis in AD. In this review, we discuss emerging evidence for therapeutic and immunomodulatory functions of TSPO in AD, and new tools for studying TSPO in the brain.</p></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"224 ","pages":"Pages 120-131"},"PeriodicalIF":3.3000,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300908424001627/pdfft?md5=30438a083c4bbbabad7f5d915d55d63f&pid=1-s2.0-S0300908424001627-main.pdf","citationCount":"0","resultStr":"{\"title\":\"The mitochondrial translocator protein (TSPO) in Alzheimer's disease: Therapeutic and immunomodulatory functions\",\"authors\":\"\",\"doi\":\"10.1016/j.biochi.2024.07.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The translocator protein (TSPO) has been widely investigated as a PET-imaging biomarker of neuroinflammation and, more recently, as a therapeutic target for the treatment of neurodegenerative disease. TSPO ligands have been shown to exert neuroprotective effects in vivo and <em>in vitro</em> models of Alzheimer's disease (AD), by reducing toxic beta amyloid peptides, and attenuating brain atrophy. Recent transcriptomic and proteomic analyses, and the generation of TSPO-KO mice, have enabled new insights into the mechanistic function of TSPO in AD. Using a multi-omics approach in both TSPO-KO- and TSPO ligand-treated mice, we have demonstrated a key role for TSPO in microglial respiratory metabolism and phagocytosis in AD. In this review, we discuss emerging evidence for therapeutic and immunomodulatory functions of TSPO in AD, and new tools for studying TSPO in the brain.</p></div>\",\"PeriodicalId\":251,\"journal\":{\"name\":\"Biochimie\",\"volume\":\"224 \",\"pages\":\"Pages 120-131\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-07-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0300908424001627/pdfft?md5=30438a083c4bbbabad7f5d915d55d63f&pid=1-s2.0-S0300908424001627-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochimie\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0300908424001627\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimie","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0300908424001627","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
转运蛋白(TSPO)作为神经炎症的正电子发射计算机成像生物标志物,以及最近作为治疗神经退行性疾病的靶点,受到了广泛的研究。在阿尔茨海默病(AD)的体内和体外模型中,TSPO 配体通过减少毒性β淀粉样肽和减轻脑萎缩,被证明具有神经保护作用。最近的转录组学和蛋白质组学分析以及 TSPO-KO 小鼠的产生,使人们对 TSPO 在阿尔茨海默病中的机理功能有了新的认识。通过对 TSPO-KO 小鼠和 TSPO 配体处理小鼠进行多组学研究,我们证明了 TSPO 在 AD 中的小胶质细胞呼吸代谢和吞噬中的关键作用。在这篇综述中,我们讨论了 TSPO 在 AD 中的治疗和免疫调节功能的新证据,以及研究大脑中 TSPO 的新工具。
The mitochondrial translocator protein (TSPO) in Alzheimer's disease: Therapeutic and immunomodulatory functions
The translocator protein (TSPO) has been widely investigated as a PET-imaging biomarker of neuroinflammation and, more recently, as a therapeutic target for the treatment of neurodegenerative disease. TSPO ligands have been shown to exert neuroprotective effects in vivo and in vitro models of Alzheimer's disease (AD), by reducing toxic beta amyloid peptides, and attenuating brain atrophy. Recent transcriptomic and proteomic analyses, and the generation of TSPO-KO mice, have enabled new insights into the mechanistic function of TSPO in AD. Using a multi-omics approach in both TSPO-KO- and TSPO ligand-treated mice, we have demonstrated a key role for TSPO in microglial respiratory metabolism and phagocytosis in AD. In this review, we discuss emerging evidence for therapeutic and immunomodulatory functions of TSPO in AD, and new tools for studying TSPO in the brain.
期刊介绍:
Biochimie publishes original research articles, short communications, review articles, graphical reviews, mini-reviews, and hypotheses in the broad areas of biology, including biochemistry, enzymology, molecular and cell biology, metabolic regulation, genetics, immunology, microbiology, structural biology, genomics, proteomics, and molecular mechanisms of disease. Biochimie publishes exclusively in English.
Articles are subject to peer review, and must satisfy the requirements of originality, high scientific integrity and general interest to a broad range of readers. Submissions that are judged to be of sound scientific and technical quality but do not fully satisfy the requirements for publication in Biochimie may benefit from a transfer service to a more suitable journal within the same subject area.