Toni Mattia, Cioni Carla
Department of Biology and Biotechnology "Charles Darwin", Sapienza University, Via Alfonso Borelli 50, Rome 00161, Italy.
Mar Drugs. 2015 Oct 30;13(11):6665-86. doi: 10.3390/md13116665.
Synucleins (syns) are a family of proteins involved in several human neurodegenerative diseases and tumors. Since the first syn discovery in the brain of the electric ray Torpedo californica, members of the same family have been identified in all vertebrates and comparative studies have indicated that syn proteins are evolutionary conserved. No counterparts of syns were found in invertebrates suggesting that they are vertebrate-specific proteins. Molecular studies showed that the number of syn members varies among vertebrates. Three genes encode for α-, β- and γ-syn in mammals and birds. However, a variable number of syn genes and encoded proteins is expressed or predicted in fish depending on the species. Among biologically verified sequences, four syn genes were identified in fugu, encoding for α, β and two γ (γ1 and γ2) isoforms, whereas only three genes are expressed in zebrafish, which lacks α-syn gene. The list of "non verified" sequences is much longer and is often found in sequence databases. In this review we provide an overview of published papers and known syn sequences in agnathans and fish that are likely to impact future studies in this field. Indeed, fish models may play a key role in elucidating some of the molecular mechanisms involved in physiological and pathological functions of syn proteins.
突触核蛋白(syns)是一类与多种人类神经退行性疾病和肿瘤相关的蛋白质。自从在加州电鳐的大脑中首次发现突触核蛋白以来,在所有脊椎动物中都鉴定出了该蛋白家族的成员,比较研究表明突触核蛋白在进化上是保守的。在无脊椎动物中未发现突触核蛋白的对应物,这表明它们是脊椎动物特有的蛋白质。分子研究表明,突触核蛋白成员的数量在脊椎动物中有所不同。在哺乳动物和鸟类中,有三个基因分别编码α-、β-和γ-突触核蛋白。然而,根据物种的不同,鱼类中表达或预测的突触核蛋白基因和编码蛋白的数量也有所不同。在经过生物学验证的序列中,在河豚中鉴定出了四个突触核蛋白基因,分别编码α、β和两种γ(γ1和γ2)异构体,而在斑马鱼中只表达三个基因,斑马鱼缺乏α-突触核蛋白基因。“未经验证”的序列列表要长得多,并且经常在序列数据库中出现。在这篇综述中,我们概述了已发表的论文以及在无颌类动物和鱼类中已知的突触核蛋白序列,这些可能会影响该领域未来的研究。事实上,鱼类模型可能在阐明突触核蛋白生理和病理功能所涉及的一些分子机制方面发挥关键作用。