State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica& Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica& Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; NHC Key Laboratory of Drug Addiction Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Pharmacol Res. 2021 Aug;170:105541. doi: 10.1016/j.phrs.2021.105541. Epub 2021 Mar 10.
Diversiform ways of intercellular communication are vital links in maintaining homeostasis and disseminating physiological states. Among intercellular bridges, tunneling nanotubes (TNTs) discovered in 2004 were recognized as potential pharmacology targets related to the pathogenesis of common or infrequent neurodegenerative disorders. The neurotoxic aggregates in neurodegenerative diseases including scrapie prion protein (PrPSc), mutant tau protein, amyloid-beta (Aβ) protein, alpha-synuclein (α-syn) as well as mutant Huntington (mHTT) protein could promote TNT formation via certain physiological mechanisms, in turn, mediating the intercellular transmission of neurotoxicity. In this review, we described in detail the skeleton, the formation, the physicochemical properties, and the functions of TNTs, while paying particular attention to the key role of TNTs in the transport of pathological proteins during neurodegeneration.
细胞间通讯的多种方式是维持内稳态和传播生理状态的重要环节。在细胞间连接中，2004 年发现的隧道纳米管（TNT）被认为是与常见或罕见神经退行性疾病发病机制相关的潜在药理学靶点。神经退行性疾病中的神经毒性聚集物，包括瘙痒朊病毒蛋白（PrPSc）、突变 tau 蛋白、淀粉样β（Aβ）蛋白、α-突触核蛋白（α-syn）以及突变亨廷顿（mHTT）蛋白，可能通过某些生理机制促进 TNT 的形成，进而介导神经毒性的细胞间传递。在这篇综述中，我们详细描述了 TNT 的骨架、形成、物理化学性质和功能，同时特别关注 TNT 在神经退行性变过程中病理性蛋白运输中的关键作用。
